| 1. |
- Bryl-Górecka, Paulina, et al.
(författare)
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Bilberry Supplementation after Myocardial Infarction Decreases Microvesicles in Blood and Affects Endothelial Vesiculation
- 2020
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Ingår i: Molecular Nutrition & Food Research. - : Wiley-VCH Verlagsgesellschaft. - 1613-4125 .- 1613-4133. ; 64:20
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Diet rich in bilberries is considered cardioprotective, but the mechanisms of action are poorly understood. Cardiovascular disease is characterized by increased proatherogenic status and high levels of circulating microvesicles (MVs). In an open-label study patients with myocardial infarction receive an 8 week dietary supplementation with bilberry extract (BE). The effect of BE on patient MV levels and its influence on endothelial vesiculation in vitro is investigated.Methods and results: MVs are captured with acoustic trapping and platelet-derived MVs (PMVs), as well as endothelial-derived MVs (EMVs) are quantified with flow cytometry. The in vitro effect of BE on endothelial extracellular vesicle (EV) release is examined using endothelial cells and calcein staining. The mechanisms of BE influence on vesiculation pathways are studied by Western blot and qRT-PCR. Supplementation with BE decreased both PMVs and EMVs. Furthermore, BE reduced endothelial EV release, Akt phosphorylation, and vesiculation-related gene transcription. It also protects the cells from P2X(7)-induced EV release and increase in vesiculation-related gene expression.Conclusion: BE supplementation improves the MV profile in patient blood and reduces endothelial vesiculation through several molecular mechanisms related to the P2X(7)receptor. The findings provide new insight into the cardioprotective effects of bilberries.
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| 2. |
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| 3. |
- Saetrum Opgaard, Ole, et al.
(författare)
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Endocardial expression and functional characterization of endothelin-1
- 2001
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Ingår i: Molecular and Cellular Biochemistry. - 0300-8177. ; 224:1-2, s. 151-158
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Tidskriftsartikel (refereegranskat)abstract
- Endothelin-1 (ET-1), a 21 amino acid peptide exerts a wide range of biological activities including vasoconstriction, mitogenesis and inotropic effects on the heart. In this study, we examined whether endocardial endothelial cells express ET-1 and evaluated its functional properties. Using immunofluorescence localization method, we demonstrated cytoplasmic staining of ET-1 in the human endocardial endothelial cells from the right atrium and left ventricle. Employing reverse transcriptase polymerase chain reaction (RT-PCR) expression of ET-1 mRNA and its receptors ET(A) and ET(B) mRNAs were found in human myocardial as well as in endocardial endothelial cells. Biological activity of endocardial endothelial cells derived ET-1 was established as the conditioned media obtained from cultured porcine endocardial endothelial cells induced a slowly developing, strong and long-lasting contraction of circular rat aortic segments, with similar characteristics to that obtained with exogenous ET-1. Furthermore, the selective endothelin-A receptor antagonist, FR 139317, blocked the conditioned media induced contractions. Our results suggest that endocardial endothelial cells express and release biologically active ET-1 which could play a pivotal role in the regulation of myocardial contractility as well as a circulatory peptide may further act in other peripheral target organs.
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| 4. |
- Akhtar, Zubair, et al.
(författare)
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Optimal timing of influenza vaccination among patients with acute myocardial infarction - Findings from the IAMI trial
- 2023
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Ingår i: Vaccine. - : Elsevier. - 0264-410X .- 1873-2518. ; 41:48, s. 7159-7165
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Tidskriftsartikel (refereegranskat)abstract
- Influenza vaccination reduces the risk of adverse cardiovascular events. The IAMI trial randomly assigned 2571 patients with acute myocardial infarction (AMI) to receive influenza vaccine or saline placebo during their index hospital admission. It was conducted at 30 centers in 8 countries from October 1, 2016 to March 1, 2020. In this post-hoc exploratory sub-study, we compare the trial outcomes in patients receiving early season vaccination (n = 1188) and late season vaccination (n = 1344). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), or stent thrombosis at 12 months. The cumulative incidence of the primary and key secondary endpoints by randomized treatment and early or late vaccination was estimated using the Kaplan-Meier method. In the early vaccinated group, the primary composite endpoint occurred in 36 participants (6.0%) assigned to influenza vaccine and 49 (8.4%) assigned to placebo (HR 0.69; 95% CI 0.45 to 1.07), compared to 31 participants (4.7%) assigned to influenza vaccine and 42 (6.2%) assigned to placebo (HR 0.74; 95% CI 0.47 to 1.18) in the late vaccinated group (P = 0.848 for interaction on HR scale at 1 year). We observed similar estimates for the key secondary endpoints of all-cause death and CV death. There was no statistically significant difference in vaccine effectiveness against adverse cardiovascular events by timing of vaccination. The effect of vaccination on all-cause death at one year was more pronounced in the group receiving early vaccination (HR 0.50; 95% CI, 0.29 to 0.86) compared late vaccination group (HR 0.75; 35% CI, 0.40 to 1.40) but there was no statistically significant difference between these groups (Interaction P = 0.335). In conclusion, there is insufficient evidence from the trial to establish whether there is a difference in efficacy between early and late vaccination but regardless of vaccination timing we strongly recommend influenza vaccination in all patients with cardiovascular diseases.
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| 5. |
- Edvinsson, Lars, et al.
(författare)
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Neuropeptide Y in sympathetic co-transmission: recent advances in the search for neuropeptide Y antagonists
- 1994
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Ingår i: Pharmacology and Toxicology. - 1600-0773. ; 74:4-5, s. 193-201
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Tidskriftsartikel (refereegranskat)abstract
- Since the discovery of neuropeptide Y which is co-stored and co-operate with noradrenaline (NA) in sympathetic nerve fibers, several scientific groups have searched for structures with neuropeptide Y antagonistic properties. Research has mainly focused on various peptide fragments which originate from or are related to the neuropeptide Y sequence. Some non-peptide antagonists have been proposed but they are mostly of low potency and non-selective. Our recent observations that alpha-trinositol (D-myo-inositol 1.2.6-trisphosphate) is an inhibitor of neuropeptide Y effects will hopefully lead to the development of useful non-peptide neuropeptide Y inhibitors. As a novel approach the highly selective approach of down-regulating neuropeptide Y receptors with antisense oligodeoxynucleotides is also discussed. Neuropeptide Y antagonistic agents would help us to understand the physiological role of neuropeptide Y and may serve as useful medication in circulation disorders.
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| 6. |
- Erlinge, David, et al.
(författare)
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Mitogenic effects of ATP on vascular smooth muscle cells vs. other growth factors and sympathetic cotransmitters
- 1993
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Ingår i: American Journal of Physiology - Heart and Circulatory Physiology. - 1522-1539. ; 265:4, s. 1089-1097
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Tidskriftsartikel (refereegranskat)abstract
- The sympathetic nervous system has been shown to exert a trophic influence on vascular smooth muscle cells (VSMC). Therefore, we studied the growth-regulating effects of the sympathetic cotransmitters ATP, neuropeptide Y (NPY), and norepinephrine (NE). ATP in concentrations of 1-100 microM greatly increased the incorporation of [3H]thymidine in VSMC from rat aorta and vena cava. ATP also increased cell number and total protein content. The maximal effect on [3H]thymidine incorporation was greater than for epidermal growth factor (20 ng/ml) or insulin (1 microgram/ml) and approximately one-half that of 10% fetal calf serum. The potency series of other nucleotides and analogues of ATP was ATP > beta, gamma-methyleneATP (AMP-PCP) > ADP > adenosine > alpha, beta- methyleneATP (AMP-CPP) > 2-methylthioATP, indicating involvement of a P2 receptor, however, it does not meet proposed pharmacological criteria of either the P2x or P2y subclass. Several proposed P2 receptor antagonists were without effect. The effect of ATP could be mediated by a "nucleotide receptor," since UTP also stimulated [3H]thymidine incorporation. In our model, there was a strong correlation between the mitogenic effects of ATP, AMP-CPP, AMP-PCP, and UTP and their ability to stimulate influx of extracellular Ca2+ (Ca2+o). Moreover, the mitogenic effect of ATP was increased by high concentrations of Ca2+o. Taken together with data showing the lack of involvement of several other second-messenger systems, this indicates a critical role for Ca2+o in mediating the mitogenic effects of ATP. Amiloride, known to inhibit the action of several growth factors, also inhibited ATP-induced mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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| 7. |
- Hou, M, et al.
(författare)
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Angiotensin II type 1 receptors stimulate protein synthesis in human cardiac fibroblasts via a Ca2+-sensitive PKC-dependent tyrosine kinase pathway
- 2000
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Ingår i: Acta Physiologica Scandinavica. - 0001-6772. ; 168:2, s. 301-309
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the present study was to investigate the proliferative effects of Ang II in human cardiac fibroblasts. The effects of Ang II in human cardiac fibroblasts on the 3H-thymidine incorporation, the cell number, the 3H-leucine incorporation and the total protein content were measured. The expression of receptor mRNA was performed by reverse transcription-polymerase chain reaction (RT-PCR). Ang II increased 3H-leucine incorporation in a concentration-dependent manner but not 3H-thymidine incorporation in primary cultures of human cardiac fibroblasts. The maximum effect (24 +/- 3% over control) was obtained at a concentration of 10 nM. There were no significant alterations of cell number or total protein content, suggesting that Ang II stimulated protein synthesis but did not induce hypertrophy. The accumulation of 3H-leucine was blocked by the AT1 receptor antagonist candesartan but not by the AT2 receptor antagonist PD123319. By using RT-PCR, both AT1 and AT2 receptors mRNA were found to be expressed in human cardiac fibroblasts. The selective MAPKK inhibitor PD098059, the protein kinase C inhibitor K252a or the phospholipase C inhibitor U73122 did not significantly inhibit Ang II augmented 3H-leucine incorporation. However, this was significantly blocked by the Ca2+-dependent protein kinase C inhibitor GO6976, the non-selective protein kinase inhibitor staurosporine and the tyrosine kinase inhibitor tyrphostin 25. The effects of Ang II were unaffected by the Gi-protein blocker pertussis toxin, indicating a Gi-protein-independent pathway. Ang II was synergistic with insulin but showed no significant increase on 3H-leucine incorporation when combined with PDGF or EGF. In summary, Ang II stimulates protein synthesis through AT1 receptors in human cardiac fibroblasts, but has no hypertrophic or hyperplastic effect. The response is mediated by a MAPKK-independent and Ca2+-sensitive PKC-dependent pathway.
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| 8. |
- Hou, Mingyan, et al.
(författare)
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Increase in cardiac P2X1-and P2Y2-receptor mRNA levels in congestive heart failure
- 1999
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Ingår i: Life Sciences. - 1879-0631. ; 65:11, s. 1195-1206
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Tidskriftsartikel (refereegranskat)abstract
- We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X1). Among the P2Y-receptors the P2Y6-receptor was most abundantly expressed (P2Y6 > P2Y1 > P2Y2 = P2Y4 > P2X1). A prominent change was seen for the P2X1- and P2Y2-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y1-, P2Y4- and P2Y6-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X1-, P2Y1-, P2Y2-, P2Y6- and P2Y11-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y4-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y2-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.
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| 9. |
- Khoshnood, Ardavan, et al.
(författare)
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Effect of oxygen therapy on chest pain in patients with ST elevation myocardial infarction : results from the randomized SOCCER trial
- 2018
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 52:2, s. 69-73
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Tidskriftsartikel (refereegranskat)abstract
- Objective. Oxygen (O2) have been a cornerstone in the treatment of acute myocardial infarction. Studies have been inconclusive regarding the cardiovascular and analgesic effects of oxygen in these patients. In the SOCCER trial, we compared the effects of oxygen treatment versus room air in patients with ST-elevation myocardial infarction (STEMI). There was no difference in myocardial salvage index or infarct size assessed with cardiac magnetic resonance imaging. In the present subanalysis, we wanted to evaluate the effect of O2 on chest pain in patients with STEMI. Design. Normoxic patients with first time STEMI were randomized in the ambulance to standard care with 10 l/min O2 or room air until the end of the percutaneous coronary intervention (PCI). The ambulance personnel noted the patients´ chest pain on a visual analog scale (VAS; 1-10) before randomization and after the transport but before the start of the PCI, and also registered the amount of morphine given. Results. 160 patients were randomized to O2 (n = 85) or room air (n = 75). The O2 group had a higher median VAS at randomization than the air group (7.0 ± 2.3 vs 6.0 ± 2.9; p = .02) and also received a higher median total dose of morphine (5.0 mg ± 4.4 vs 4.0 mg ± 3.7; p = .02). There was no difference between the O2 and air groups in VAS at the start of the PCI (4.0 ± 2.4 vs 3.0 ± 2.5; p = .05) or in the median VAS decrease from randomization to the start of the PCI (−2.0 ± 2.2 vs −1.0 ± 2.9; p = .18). Conclusion. Taken together with previously published data, these results do not support a significant analgesic effect of oxygen in patients with STEMI. European Clinical Trials Database (EudraCT): 2011-001452-11. ClinicalTrials.gov Identifier: NCT01423929
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| 10. |
- Khoshnood, Ardavan, et al.
(författare)
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Effect of oxygen therapy on myocardial salvage in ST elevation myocardial infarction : the randomized SOCCER trial
- 2018
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Ingår i: European Journal of Emergency Medicine. - 0969-9546. ; 25:2, s. 78-84
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Recent studies suggest that administration of O2 in patients with acute myocardial infarction may have negative effects. With the use of cardiac MRI (CMR), we evaluated the effects of supplemental O2 in patients with ST elevation myocardial infarction (STEMI) accepted for acute percutaneous coronary intervention (PCI).MATERIALS AND METHODS: This study was a randomized-controlled trial conducted at two university hospitals in Sweden. Normoxic STEMI patients were randomized in the ambulance to either supplemental O2 (10 l/min) or room air until the conclusion of the PCI. CMR was performed 2-6 days after the inclusion. The primary endpoint was the myocardial salvage index assessed by CMR. The secondary endpoints included infarct size and myocardium at risk.RESULTS: At inclusion, the O2 (n=46) and air (n=49) patient groups had similar patient characteristics. There were no significant differences in myocardial salvage index [53.9±25.1 vs. 49.3±24.0%; 95% confidence interval (CI): -5.4 to 14.6], myocardium at risk (31.9±10.0% of the left ventricle in the O2 group vs. 30.0±11.8% in the air group; 95% CI: -2.6 to 6.3), or infarct size (15.6±10.4% of the left ventricle vs. 16.0±11.0%; 95% CI: -4.7 to 4.1).CONCLUSION: In STEMI patients undergoing acute PCI, we found no effect of high-flow oxygen compared with room air on the size of ischemia before PCI, myocardial salvage, or the resulting infarct size. These results support the safety of withholding supplemental oxygen in normoxic STEMI patients.
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