| 1. |
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| 2. |
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| 3. |
- Ahlin, Fredrik, et al.
(författare)
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MicroRNAs as circulating biomarkers in acute coronary syndromes: A review
- 2016
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Ingår i: Vascular pharmacology. - : ELSEVIER SCIENCE INC. - 1537-1891 .- 1879-3649. ; 81, s. 15-21
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Forskningsöversikt (refereegranskat)abstract
- Coronary artery disease (CAD) and its complications remain the most common cause of death worldwide. Cardiac troponins (cTn) are standard biomarkers used today for diagnosis and risk stratification of myocardial infarction (MI). Increasing efforts are made to develop additional, new biomarkers for more effective and safe rule-in and rule-out of MI patients at the emergency department. During the past decade, microRNAs (miRNAs) have emerged as new, potential diagnostic biomarkers in several diseases, including MI. In this review, we aimed to summarize some of the prominent studies in the field, and discuss the potential value of miRNAs in the diagnosis of MI. (C) 2016 Elsevier Inc. All rights reserved.
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| 4. |
- Alajbegovic, Azra, et al.
(författare)
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MRTFA overexpression promotes conversion of human coronary artery smooth muscle cells into lipid-laden foam cells
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Smooth muscle cells contribute significantly to lipid-laden foam cells in atherosclerotic plaques. However, the underlying mechanisms transforming smooth muscle cells into foam cells are poorly understood. The purpose of this study was to gain insight into the molecular mechanisms regulating smooth muscle foam cell formation. Approach and results: Using human coronary artery smooth muscle cells we found that the transcriptional co-activator MRTFA promotes lipid accumulation via several mechanisms, including direct transcriptional control of LDL receptor, enhanced fluid-phase pinocytosis and reduced lipid efflux. Inhibition of MRTF activity with CCG1423 and CCG203971 significantly reduced lipid accumulation. Furthermore, we demonstrate enhanced MRTFA expression in vascular remodeling of human vessels. Conclusions: This study demonstrates a novel role for MRTFA as an important regulator of lipid homeostasis in vascular smooth muscle cells. Thus, MRTFA could potentially be a new therapeutic target for inhibition of vascular lipid accumulation.
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| 5. |
- Arévalo-Martinez, Marycarmen, et al.
(författare)
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Myocardin related transcription factor and galectin-3 drives lipid accumulation in human blood vessels
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Ingår i: Vascular Pharmacology. - 1537-1891.
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Diabetes and hypertension are important risk factors for vascular disease, including atherosclerosis. A driving factor in this process is lipid accumulation in smooth muscle cells of the vascular wall. The glucose- and mechano-sensitive transcriptional coactivator, myocardin-related transcription factor A (MRTF-A/MKL1) can promote lipid accumulation in cultured human smooth muscle cells and contribute to the formation of smooth muscle-derived foam cells. The purpose of this study was to determine if intact human blood vessels ex vivo can be used to evaluate lipid accumulation in the vascular wall, and if this process is dependent on MRTF and/or galectin-3/LGALS3. Galectin-3 is an early marker of smooth muscle transdifferentiation and a potential mediator for foam cell formation and atherosclerosis.APPROACH AND RESULTS: Human mammary arteries and saphenous veins were exposed to altered cholesterol and glucose levels in an organ culture model. Accumulation of lipids, quantified by Oil Red O, was increased by cholesterol loading and elevated glucose concentrations. Pharmacological inhibition of MRTF with CCG-203971 decreased lipid accumulation, whereas adenoviral-mediated overexpression of MRTF-A had the opposite effect. Cholesterol-induced expression of galectin-3 was decreased after inhibition of MRTF. Importantly, pharmacological inhibition of galectin-3 with GB1107 reduced lipid accumulation in the vascular wall after cholesterol loading.CONCLUSION: Ex vivo organ culture of human arteries and veins can be used to evaluate lipid accumulation in the intact vascular wall, as well as adenoviral transduction and pharmacological inhibition. Although MRTF and galectin-3 may have beneficial, anti-inflammatory effects under certain circumstances, our results, which demonstrate a significant decrease in lipid accumulation, support further evaluation of MRTF- and galectin-3-inhibitors for therapeutic intervention against atherosclerotic vascular disease.
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| 6. |
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| 7. |
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| 8. |
- Bosmans, Laura A., et al.
(författare)
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Glucocorticoid induced TNF receptor family-related protein (GITR) – A novel driver of atherosclerosis
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 139
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Forskningsöversikt (refereegranskat)abstract
- Atherosclerosis is a lipid-driven, chronic inflammatory disease. In spite of efficient lipid lowering treatments, such as statins and PCSK9 inhibitors, patients, especially those with elevated inflammatory biomarkers, still have a significant residual cardiovascular disease risk. Novel drugs targeting inflammatory mediators are needed to further reduce this residual risk. Agonistic immune checkpoint proteins, including CD86, CD40L and CD40, have been shown to be drivers of atherosclerosis. Recently, glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR), a co-stimulatory immune checkpoint protein, was identified to be pivotal in cardiovascular disease. Cardiovascular patients have elevated soluble GITR plasma levels compared to healthy controls. Furthermore, in human carotid endarterectomy plaques, GITR expression was higher in plaques from symptomatic compared to asymptomatic patients and correlated with features of plaque vulnerability. Moreover, depleting GITR reduced atherosclerotic plaque development in mice. GITR-deficient monocytes and macrophages exhibited less inflammatory potential and reduced migratory capacity. In this review, we discuss GITR's effects on various immune cells, mechanisms, signalling pathways and finally GITR's potential as a novel drug target in atherosclerosis.
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| 9. |
- Cao, Yong-Xiao, et al.
(författare)
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Ligustilide induces vasodilatation via inhibiting voltage dependent calcium channel and receptor-mediated Ca(2+) influx and release.
- 2006
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 45:3, s. 171-176
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of the present study was to investigate the effect of ligustilide on vasodilatation in rat mesenteric artery and the mechanisms responsible for it. Isometric tension of rat mesenteric artery rings was recorded by a sensitive myograph system in vitro. The results showed that ligustilide at concentrations more than 10 mu M relaxed potassium chloride (KCl)-preconstricted rat mesenteric artery in a con centration-dependent manner. The vasodilatation effect of ligustilide was not dependent on endothelium. Ligustilide rightwards shifted concentration-response curves induced by KCl, calcium chloride (CaCl2), noradrenaline (NA) or 5-hydroxytryptamine (5-HT) in a non-parallel manner. This suggests that the vasodilatation effects were most likely via voltage-dependent calcium channel (VDCC) and receptor-operated calcium channel (ROCC). Propranolol, glibenclamide, tetraethylammonium and barium chloride did not affect the vasodilation induced by ligustilide, showing that beta-adrenoceptor, ATP sensitive potassium channel, calcium-activated potassium channel and inwardly rectifying potassium channel were not involved in the vasodilatation. Ligustilide concentration-dependently inhibited the vasoconstriction induced by NA or CaCl2 in Ca2+-free medium, indicating that the vasodilatation relates to inhibition of extracellular Ca2+ influx through VDCC and ROCC, and intracellular Ca2+ release from Ca2+ store. Since caffeine-induced contraction was inhibited by ligustilide, inhibition of intracellular Ca2+ released by ligustilide occurred via the ryanodine receptors. Our results suggest that ligustilide induces vasodilatation in rat mesenteric artery by inhibiting the VDCC and ROCC, and receptor-mediated Ca2+ influx and release. (c) 2006 Elsevier Inc. All rights reserved.
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| 10. |
- Chen, Yulong, et al.
(författare)
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Homocysteine regulates endothelin type B receptors in vascular smooth muscle cells
- 2016
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 87, s. 100-109
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Tidskriftsartikel (refereegranskat)abstract
- Vascular smooth muscle endothelin type B (ETB) receptor is involved in the pathogenesis of cardiovascular diseases (CVDs). Hyperhomocysteinemia is an independent risk factor for CVDs. The present study was designed to examine the hypothesis that homocysteine (Hcy) up-regulates vascular smooth muscle ETB receptors. In vitro experiments were performed in rat superior mesenteric artery (SMA) and vascular smooth muscle cells (VSMCs). The rat SMA or VSMCs were cultured in serum-free medium for 24 h in the presence and absence of Hcy with or without specific inhibitors for the ERK1/2 signaling pathway and NF-κB. In vivo, the rats received subcutaneous injections of Hcy in the presence or absence of specific inhibitors for the ERK1/2 signaling pathway (U0126) for 3 weeks. Levels of protein expression were determined using Western blot analysis. The contractile responses to sarafotoxin 6c (an ETB receptor agonist) were studied using a sensitive myograph. The blood pressure of the rats was measured via a noninvasive tail-cuff plethysmography method. The results from in vitro experiments showed that Hcy concentration-dependently increased the ETB receptor-mediated contractile responses, and up-regulated ETB receptor expression, in rat SMA. Blockage of the ERK1/2 signaling pathway and NF-κB using the MEK1/2 inhibitor (PD98059 and U0126) or IκB kinase inhibitor (wedelolactone) significantly abolished Hcy-induced up-regulation of ETB receptor. Finally, we used VSMCs as a cellular model to further validate our finding. In vivo study found that hyperhomocysteinemia up-regulated ETB receptor expression, and elevated the blood pressure of rats via the ERK1/2 signaling pathway. In conclusion, Hcy up-regulated vascular smooth muscle ETB receptor via activation of the ERK1/2 signaling pathway and NF-κB.
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| 11. |
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| 12. |
- Claesson-Welsh, Lena
(författare)
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VEGF receptor signal transduction - A brief update
- 2016
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Ingår i: Vascular pharmacology. - : Elsevier BV. - 1537-1891 .- 1879-3649. ; 86, s. 14-17
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Forskningsöversikt (refereegranskat)abstract
- Vascular endothelial growth factor (VEGF) signal transduction through receptor tyrosine lcinases VEGF receptor 1, -2 and -3 is of crucial importance for monocytes/macrophages, blood vascular endothelial and lymphatic endothelial cells both in physiology and in a number of pathologies notably cancer. This brief review summarizes the current status of VEGF receptor signaling with emphasis on in vivo data.
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| 13. |
- Edsfeldt, Andreas, et al.
(författare)
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Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk
- 2023
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Ingår i: Vascular Pharmacology. - 1537-1891. ; 152
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Tidskriftsartikel (refereegranskat)abstract
- Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. Results: During 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. Conclusions: Our findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.
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| 14. |
- Elovsson, Sofia, et al.
(författare)
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Evaluation of nasal barrier dysfunction at acute- and late-phase reactions in a guinea pig model of allergic rhinitis
- 2005
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 43:4, s. 267-276
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Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis is a common disease characterized by the symptoms of pruritus, sneezing, hypersecretion and nasal blockage. Increased mucosal barrier permeability has been suggested to be an indicator for the severity of allergic rhinitis. This study investigates the passage of radiolabelled albumin from the nasal mucosal circulation into the lumen in guinea pigs intraperitoneally sensitized and intranasally challenged with antigen. In order to characterize the allergic rhinitis model, we evaluated a number of potential influencing factors in nasal plasma exudation, including antigen doses, volumes of antigen solution used, and animal position during the nasal lavage, and the conditions of nasal lavage. The number of eosinophils and levels of histamine and leukotriene B4 in the nasal lavage and eosinophils in the nasal mucosa were determined at the early and late phases after antigen challenge. We also compared the effects of topical nasal treatments for allergic rhinitis on nasal inflammatory responses. Our results demonstrate that, in the guinea pig nasal mucosa, topical challenge with antigens induces plasma exudation and histamine release at the acute-phase reaction, and plasma exudation and eosinophil infiltration at the late-phase reaction. These changes are similar to those reported in human allergic rhinitis. Alterations of nasal plasma exudation, histamine release and eosinophil influx were dependent upon the concentrations and volumes of antigens. An antihistamine inhibited the acute-phase reaction partially, whereas budesonide inhibited effects at the late-phase reaction. We suggest that this model of guinea pig allergic rhinitis with the early and late responses may be useful for high-throughout screening of new drugs.
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| 15. |
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| 16. |
- Geng, Yong-Jian, et al.
(författare)
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Linking immunity to atherosclerosis: Implications for vascular pharmacology - A tribute to Goran K. Hansson
- 2012
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Ingår i: Vascular pharmacology. - : Elsevier. - 1537-1891 .- 1879-3649. ; 56:1-2, s. 29-33
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Forskningsöversikt (refereegranskat)abstract
- For the past decade, we have deepened our understanding of the pathogenesis of atherosclerosis, a chronic arterial disease that causes cardiac and cerebral infarction and peripheral vascular disorders. Because of this extended understanding, more effective strategies for prevention and treatment of this disease are emerging. One of the fundamental mechanisms that lead to progress or regression in atherosclerosis, thus influencing its life-threatening complications, occurs through functional changes in vascular immunity and inflammation. This review briefly summarizes the discoveries in basic and translational sciences in this area and recent advances in clinical medicine against atherosclerotic vascular diseases.
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| 17. |
- Hafizi, Sassan, et al.
(författare)
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Differential effects of rapamycin, cyclosporine A, and FK506 on human coronary artery smooth muscle cell proliferation and signalling
- 2004
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 41:4-5, s. 167-176
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Tidskriftsartikel (refereegranskat)abstract
- Background: Immunosuppressive agents are at the forefront of preventing organ rejection after transplantation. However, their effects on vascular smooth muscle cell-mediated intimal hyperplasia that occurs in post-transplant coronary artery disease are less well known. Methods and results: We investigated the in vitro effects of three immunosuppressive agents cyclosporine A (CsA), FK506 (tacrolimus), and rapamycin (sirolimus, Rapa) on cultured human coronary artery smooth muscle cells (cSMC). CsA inhibited both platelet-derived growth factor (PDGF)-stimulated DNA synthesis and serum-induced proliferation at high concentrations (greater than or equal to 1000 ng/ ml). The growth-inhibitory effect of CsA was not altered by anti-TGF-beta neutralising antibodies nor was autocrine TGF-beta release detected in CsA-treated culture medium. At inhibitory doses, CsA inhibited ERK kinase activation by PDGF, although cytotoxicity was also apparent. Most notably, CsA visibly prevented PDGF-induced altered cell morphology. Rapa was a highly potent and effective inhibitor of cSMC proliferation (reduction in DNA synthesis by >50% from 0.01 ng/ml), acting through inhibition of 70kDa S6 kinase (p70(S6k)). FK506 (1-1000 ng/ml) did not affect cSMC proliferation alone, although a greater than or equal to250-fold excess of FK506 over Rapa completely reversed the inhibitory effect of Rapa, confirming that these two agents share a common intracellular receptor, the FK506-binding protein (FKBP). Conclusion: Rapa is a powerful inhibitor of cSMC proliferation, while CsA slighly inhibits cSMC proliferation, although only at higher concentrations that may be toxic. These results indicate that therapeutic immunosuppression with Rapa may be additionally useful in prevention or delay of posttransplant coronary artery disease. (C) 2004 Elsevier Inc. All rights reserved.
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| 18. |
- Henrohn, Dan, et al.
(författare)
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Changes in plasma levels of asymmetric dimethylarginine, symmetric dimethylarginine, and arginine after a single dose of vardenafil in patients with pulmonary hypertension
- 2015
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Ingår i: Vascular pharmacology. - : Elsevier BV. - 1537-1891 .- 1879-3649. ; 73, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated whether vardenafil, a phosphodiesterase-5 inhibitor, alters plasma levels of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and arginine.PATIENTS AND METHODS: ADMA, SDMA, and arginine were measured (0-540min) in 12 patients with pulmonary hypertension after a single oral dose of vardenafil. Invasive hemodynamic data were collected at baseline and after 60min.RESULTS: A reduction in ADMA was observed at 30 and 45min with a median change of -11.1% (P=0.021) and -12.5% (P=0.002). SDMA decreased with a median -5.3% change (P=0.032) at 45min. An increase in arginine, median 40.3% (P=0.002), 45.0% (P=0.010), and 77.1% (P=0.008) was observed at 120, 300, and 540min respectively. An increase in the arginine/ADMA ratio, median 11.7% (P=0.012), 32.5% (P=0.003), 26.5% (P=0.021), 33% (P=0.007), 48.5% (P=0.007), and 63.1% (P=0.008) was observed at 15, 45, 60, 120, 300, and 540min respectively. There was a positive correlation between vardenafil exposure and the percent change in the arginine/ADMA ratio from baseline to 540min (r=0.80; P=0.01). A correlation between baseline mean right atrial pressure (mRAP) and baseline ADMA (r=0.65; P=0.023), and baseline SDMA (r=0.61; P=0.035) was observed. A correlation between the baseline arginine/ADMA ratio and baseline cardiac output (CO) (r=0.59; P=0.045) and baseline cardiac index (CI) (r=0.61; P=0.036) was observed. Baseline arginine/ADMA ratio correlated with baseline mRAP (r=-0.79; P=0.002). A correlation between change (0-60min) in CI and change in arginine (r=0.77; P=0.003) as well as change in the arginine/ADMA ratio (r=0.61; P=0.037) was observed.CONCLUSIONS: Vardenafil induced changes in ADMA, SDMA, arginine, and the arginine/ADMA ratio in patients with PH. An increase in arginine and the arginine/ADMA ratio was associated with improvement in CI.
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| 19. |
- Holm, H, et al.
(författare)
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Beta-blocker therapy and risk of vascular dementia: A population-based prospective study
- 2020
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Ingår i: Vascular pharmacology. - : ELSEVIER SCIENCE INC. - 1537-1891 .- 1879-3649. ; 125
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Tidskriftsartikel (refereegranskat)abstract
- There are a few studies that report cognitive impairment as a complication of treatment with beta-blockers. We aimed to evaluate the longitudinal association between use of beta-blockers, as a class, and incident risk of all-cause dementia, vascular dementia, Alzheimers and mixed dementia in the prospective population-based Malmo Preventive Project. We included 18,063 individuals (mean age 68.2, males 63.4%) followed up for 84,506 person-years. Dementia cases were retrieved from the Swedish National Patient Register and validated by review of medical records and neuroimaging data. We performed propensity score matching analysis, resulting in 3720 matched pairs of beta-blocker users and non-users at baseline, and multivariable Cox proportional-hazards regression. Overall, 122 study participants (1.6%) were diagnosed with dementia during the follow-up. Beta-blocker therapy was independently associated with increased risk of developing vascular dementia, regardless of confounding factors (HR: 1.72, 95%CI 1.01-3.78; p = .048). Conversely, treatment with beta-blockers was not associated with increased risk of all-cause, Alzheimers and mixed dementia (HR:1.15; 95%CI 0.80-1.66; p = .44; HR:0.85; 95%CI 0.48-1.54; P = .59 and HR:1.35; 95%CI 0.56-3.27; p = .50, respectively). We observed that use of beta-blockers, as a class, is associated with increased longitudinal risk of vascular dementia in the general elderly population, regardless of cardiovascular risk factors, prevalent or incident history of atrial fibrillation, stroke, coronary events and heart failure. Further studies are needed to confirm our findings in the general population and to explore the mechanisms underlying the relationship between use of beta-blockers and increased risk of vascular dementia.
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| 20. |
- Kostrzewska, Ama, et al.
(författare)
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Effect of nitric oxide on responses of the human uterine arteries to vasopressin
- 2008
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 48:1, s. 9-13
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Tidskriftsartikel (refereegranskat)abstract
- Nitric oxide (NO) is known to be an important relaxant of contractile activity in various muscles including the human uterine arteries. It has been suggested that NO plays a role in modulation of vascular action of arginin vasopressin (AVP), a strong vasoconstrictor of the human uterine arteries. Therefore, the purposes of this study were to investigate an involvement of endogenous NO in regulation of responses of the human intrauterine arteries to AVP and examine the effect of exogenous NO on contractions of the human intrauterine arteries evoked by AVP. Pretreatment of the artery rings with L-NA, an inhibitor of NO synthase significantly increased the resting force and enhanced the artery responses to AVP. The opposite effect has been observed after administration of 10(-6) mol/L sodium nitroprusside (SNP). Pretreatment of the artery rings with 10(-7) M CTX, a blocker of Ca2+-sensitive potassium channels with large conductance, did not change significantly their responses to ANT. Glibenclamide (1.5 10(-6) mol/L), a blocker of ATP-dependent potassium channels and apamin (10(-8) M), a specific blocker of Ca2+-sensitive potassium channels with small conductance strongly enhanced the maximum responses of the artery rings to AVP. Pretreatment with CTX significantly decreased the relaxation induced by SNP while apamin attenuated the sensitivity to SNP resulted in rightward shift of the concentration-response curve to SNP. In conclusion, this study indicates that: NO plays a role in regulation of both the vascular tone of the human intramyometrial arteries and their response to AVP. Ca2+-sensitive K+ channels with small and large conductance are involved in the SNP-induced relaxation of these arteries. The pathways of this relaxation cannot be sufficiently explained at this moment and need further investigation. (C) 2007 Elsevier Inc. All rights reserved.
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| 21. |
- Kotini, Maria Paraskevi, et al.
(författare)
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Sprouting and anastomosis in the Drosophila trachea and the vertebrate vasculature : Similarities and differences in cell behaviour
- 2019
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Ingår i: Vascular pharmacology. - : Elsevier. - 1537-1891 .- 1879-3649. ; 112, s. 8-16
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Tidskriftsartikel (refereegranskat)abstract
- Branching morphogenesis is a fascinating process whereby a simple network of biological tubes increases its complexity by adding new branches to existing ones, generating an enlarged structure of interconnected tubes. Branching morphogenesis has been studied extensively in animals and much has been learned about the regulation of branching at the cellular and molecular level. Here, we discuss studies of the Drosophila trachea and of the vertebrate vasculature, which have revealed how new branches are formed and connect (anastomose), leading to the establishment of complex tubular networks. We briefly describe the cell behaviour underlying tracheal and vascular branching. Although similar at many levels, the branching and anastomosis processes characterized thus far show a number of differences in cell behaviour, resulting in somewhat different tube architectures in these two organs. We describe the similarities and the differences and discuss them in the context of their possible developmental significance. We finish by highlighting some old and new data, which suggest that live imaging of the development of capillary beds in adult animals might reveal yet unexplored endothelial behaviour of endothelial cells.
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| 22. |
- Lindholm, Marie, et al.
(författare)
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Simvastatin stimulates macrophage interleukin-1beta secretion through an isoprenylation-dependent mechanism.
- 2007
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 46:Jul 25, s. 91-96
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Tidskriftsartikel (refereegranskat)abstract
- Statin treatment inhibits oxidized lipoprotein-induced intracellular lipid accumulation (foam cell formation) and reduces plasma levels of inflammatory markers such as interleukin-1 beta The aim of the present study was to determine if simvastatin affected lipid accumulation in macrophages incubated with aggregated low density lipoproteins (AgLDL) and whether simvastatin had a direct effect on cytokine secretion from macrophages. Simvastatin treatment did not inhibit AgLDL-induced macrophage lipid accumulation, but significantly increased the secretion of IL-1 beta and IL-8 from macrophages, whilst inhibiting the secretion of tumor necrosis factor-alpha (TNF-alpha) and having no significant effect on IL-6 secretion. Increased macrophage lipid content did not block statin-induced and IL-8 secretion. Simvastatin-stimulated IL-1 beta secretion from macrophages was inhibited by isoprenoids. We therefore hypothesized that simvastatin stimulated IL-1 beta secretion by affecting isoprenylation-dependent signaling pathways. Another possible mechanism for affecting such signaling is to impair isoprenoid transfer protein activity with specific inhibitors such as GGT1-297 and FTInhI. This treatment resulted in strong stimulation of IL-1 beta secretion that was further enhanced when exogenous IL-1 beta was present at the beginning of treatment. These data suggest an isoprenylation-dependent negative-feedback loop for macrophage IL-1 beta secretion that is inhibited by statin treatment. (c) 2006 Elsevier Inc. All rights reserved.
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| 23. |
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| 24. |
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| 25. |
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| 26. |
- Rattik, Sara, et al.
(författare)
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B cells treated with CTB-p210 acquire a regulatory phenotype in vitro and reduce atherosclerosis in apolipoprotein E deficient mice
- 2018
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 111, s. 54-61
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Intranasal immunization with a fusion protein of the ApoB100-derived peptide p210 and the cholera toxin B subunit (CTB-p210) has previously been shown to induce mucosal tolerance and reduce atherosclerosis development, but the exact mode of action remains to be elucidated. Recent studies have indicated an important role for B cells in mucosal tolerance, in particular by induction of regulatory B (Bregs) and T cells (Tregs). In this study, we aimed to investigate if transfer of B cells pulsed with CTB-p210 can protect against atherosclerosis. Method and results: First, we studied if CTB-p210 can induce Bregs and Tregs in vitro. After pulsing B cells from Apob(tm2gy)ldlr(-/-) or Apoe(-/-) mice with CTB-p210 for 1 h and co-culturing them with naive T cells for 48 h, we observed increased expression of membrane bound TGF beta/latency-associated peptide (mTGF beta/LAP) on B cells and an increased proportion of CD25(hi)FoxP3(+) Tregs. Adoptive transfer of B cells pulsed with CTB-p210 into high-fat diet-fed Apoe(-/-) mice at 8, 10 and 12 weeks of age, reduced the plaque area in the aorta at 20 weeks of age as compared with control-treated (CTB-pOVA treated B cells or PBS) mice. Moreover, mice receiving p210-CTB treated B cells had increased levels of anti-p210 IgG antibodies. Conclusion: Our observations suggest that CTB-p210 pulsed B cells acquire a regulatory phenotype and induce Tregs in vitro. Adoptive transfer of CTB-p210, but not control-treated, B cells into Apoe(-/-) mice decreased atherosclerosis development.
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| 27. |
- Shi, Changbin, et al.
(författare)
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Potential effects of PKC or protease inhibitors on acute pancreatitis-induced tissue injury in rats.
- 2007
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 46:6, s. 406-411
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Tidskriftsartikel (refereegranskat)abstract
- Background: Acute pancreatitis (AP) is still one of the severe diseases, that cause the development of multiple organ dysfunction with a high mortality. Effective therapies for AP are still limited, mainly due to unclear mechanisms by which A-P initiates both pancreatic and extrapancreatic organ injury. Methods: Protease inhibitors (aprotinin, pefabloc, trypsin inhibitor) and PKC inhibitors (polymyxin B, staurosporine) were administrated 30 min before 'induction of AP in rats. To investigate the pancreatic, systemic and lung inflammatory response and injury, plasma IL-6 and IL-10, pancreatic and pulmonary myeloperoxidase (NIPO) levels, pancreatic protease activity and phospholipase A(2) (PLA(2)) activity in ascites were measured 3 and 6 h after AP induction. Results: Pretreatment with protease inhibitors significantly prevented from AP-increased plasma levels of IL-10, pancreatic and pulmonary levels of MTO, pancreatic protease activity and the catalytic activity of PLA(2) in ascites. PKC inhibitors significantly reduced pancreatic and pulmonary levels of MTO and pancreatic protease activity. Conclusion: Inhibition of proteases in AP may be helpful in ameliorating the inflammatory reaction in both pancreatic and extrapancreatic tissues, where neutrophil involvement may be regulated by PKC and proteases.
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| 28. |
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| 29. |
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| 30. |
- Spin, JM, et al.
(författare)
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Non-coding RNAs in aneurysmal aortopathy
- 2019
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Ingår i: Vascular pharmacology. - : Elsevier BV. - 1879-3649 .- 1537-1891. ; 114, s. 110-121
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Tidskriftsartikel (refereegranskat)
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| 31. |
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| 32. |
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| 33. |
- Wågsäter, Dick, Professor, et al.
(författare)
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miR-10b promotes aortic aneurysm formation and aortic rupture in angiotensin II-induced ApoE-deficient mice
- 2021
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Ingår i: Vascular pharmacology. - : Elsevier. - 1537-1891 .- 1879-3649. ; 141
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Tidskriftsartikel (refereegranskat)abstract
- Abdominal aortic aneurysm (AAA) is associated with increased plasma levels of microRNA (miR) -10b. 5 nmols of miR-10b or miR control was administrated to Apolipoprotein E-deficient mice three days prior implantation of osmotic mini-pumps containing angiotensin II, and for three additional times once a week, which increased expression of miR-10b in plasma. Animals receiving miR-10b had a mortality rate due to aortic rupture of 61% compared to 11% in the miR controls (p < 0.05). Further, miR- 10b resulted in an increased aneurysm formation and growth (p < 0.05), which was accompanied by increased elastin degradation, neutrophil and mast cell markers (p < 0.05). In conclusion, miR-10b is functionally affecting aneurysm development and rupture and not only a marker of AAA. More mechanistic studies are required to better understand miR-10b's role in AAA formation.
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| 34. |
- Xu, Cang-Bao, et al.
(författare)
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Low density lipoprotein induces upregulation of vasoconstrictive endothelin type B receptor expression.
- 2014
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 60:1, s. 42-48
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Tidskriftsartikel (refereegranskat)abstract
- Vasoconstrictive endothelin type B (ETB) receptors promote vasospasm and ischemic cerebro- and cardiovascular diseases. The present study was designed to examine if low density lipoprotein (LDL) induces upregulation of vasoconstrictive ETB receptor expression and if extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) signal pathways are involved in this process. Rat mesenteric artery segments were organ cultured in the presence and absence of LDL with or without inhibitors for MAPK kinase 1 and 2 (MEK1/2), p38 and transcription. The upregulation of vasoconstrictive ETB receptor expression was studied using a sensitive myograph, real-time PCR and Western blot. LDL (11, 22 and 44mg protein/L) concentration-dependently induced upregulation of vasoconstrictive ETB receptor expression with increase in the receptor-mediated vasoconstriction, elevated levels of the ETB receptor mRNA and protein expressions, and activation of ERK1/2 and p38 MAPK. Blockage of ERK1/2 and p38 MAPK signal pathways using MEK1/2 inhibitors (PD98059 and U0126) or p38 inhibitors (SB203580 and SB239063) significantly abolished the LDL-induced upregulation of vasoconstrictive ETB receptor expression. Actinomycin D (general transcriptional inhibitor) almost completely inhibited the LDL effects. In conclusion, LDL induces upregulation of vasoconstrictive ETB receptor expression through activation of ERK1/2 and p38 MAPK signal pathway-dependent transcriptional mechanisms.
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| 35. |
- Yao Mattisson, Ingrid, et al.
(författare)
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Immune responses against oxidized LDL as possible targets for prevention of atherosclerosis in systemic lupus erythematosus
- 2021
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Ingår i: Vascular Pharmacology. - : Elsevier BV. - 1537-1891. ; 140
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Tidskriftsartikel (refereegranskat)abstract
- Patients suffering from systemic lupus erythematosus (SLE) are at increased risk of developing cardiovascular disease (CVD) and traditional therapies including statins provide insufficient protection. Impaired removal of apoptotic material is a common pathogenic mechanism in both SLE and atherosclerosis and is considered to be a key factor in the development of autoimmunity. Since oxidized LDL and apoptotic material bind to the same receptors, we aimed to investigate if targeting the oxidized LDL autoimmunity can affect atherosclerosis in SLE. To investigate the possible role of oxidized LDL autoimmunity in the accelerated atherosclerosis associated with SLE we used a hypercholesterolemic SLE mouse model (B6.lpr.ApoE−/− mice). Promoting LDL tolerance through mucosal immunization with an apolipoprotein B-100 peptide p45 (amino acids 661–680) and cholera toxin B-subunit fusion protein increased regulatory T cells and B cells in mesenteric lymph nodes and reduced plaque development in the aorta by 33%. Treatment with the oxidized LDL-specific antibody Orticumab reduced aortic atherosclerosis by 43%, subvalvular plaque area by 50% and the macrophage content by 31%. The present study provides support for oxLDL as a possible target for prevention of cardiovascular complications in SLE. © 2021 The Author(s)
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