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- Albinsson, Sebastian, et al.
(författare)
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Patients with bicuspid and tricuspid aortic valve exhibit distinct regional microrna signatures in mildly dilated ascending aorta
- 2017
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Ingår i: Heart and Vessels. - : Springer Science and Business Media LLC. - 0910-8327 .- 1615-2573. ; 32:6, s. 750-767
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Tidskriftsartikel (refereegranskat)abstract
- MicroRNAs are able to modulate gene expression in a range of diseases. We focused on microRNAs as potential contributors to the pathogenesis of ascending aorta (AA) dilatation in patients with stenotic tricuspid (TAV) or bicuspid aortic valve (BAV). Aortic specimens were collected from the ‘concavity’ and the ‘convexity’ of mildly dilated AAs and of normal AAs from heart transplant donors. Aortic RNA was analyzed through PCR arrays, profiling the expression of 84 microRNAs involved in cardiovascular disease. An in silico analysis identified the potential microRNA–mRNA interactions and the enriched KEGG pathways potentially affected by microRNA changes in dilated AAs. Distinct signatures of differentially expressed microRNAs are evident in TAV and BAV patients vs. donors, as well as differences between aortic concavity and convexity in patients only. MicroRNA changes suggest a switch of SMC phenotype, with particular reference to TAV concavity. MicroRNA changes potentially affecting mechanotransduction pathways exhibit a higher prevalence in BAV convexity and in TAV concavity, with particular reference to TGF-β1, Hippo, and PI3K/Akt/FoxO pathways. Actin cytoskeleton emerges as potentially affected by microRNA changes in BAV convexity only. MicroRNAs could play distinct roles in BAV and TAV aortopathy, with possible implications in diagnosis and therapy.
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| 4. |
- Forte, Amalia, et al.
(författare)
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Polyamine concentration is increased in thoracic ascending aorta of patients with bicuspid aortic valve
- 2018
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Ingår i: Heart and Vessels. - : Springer Science and Business Media LLC. - 0910-8327 .- 1615-2573. ; , s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Polyamines are cationic molecules synthesized via a highly regulated pathway, obtained from the diet or produced by the gut microbiota. They are involved in general molecular and cellular phenomena that play a role also in vascular disease. Bicuspid aortic valve (BAV) is a congenital malformation associated to a greater risk of thoracic ascending aorta (TAA) aneurysm, whose pathogenesis is not yet well understood. We focused on differential analysis of key members of polyamine pathway and on polyamine concentration in non-dilated TAA samples from patients with either stenotic tricuspid aortic valve (TAV) or BAV (diameter ≤ 45 mm), vs. normal aortas from organ donors, with the aim of revealing a potential involvement of polyamines in early aortopathy. Changes of gene expression in TAA samples were evaluated by RT-PCR. Changes of ornithine decarboxylase 1 (ODC1), a key enzyme in polyamine formation, and cationic amino acid transporter 1 (SLC7A1/CAT-1) expression were analyzed also by Western blot. ODC1 subcellular localization was assessed by immunohistochemistry. Polyamine concentration in TAA samples was evaluated by HPLC. BAV TAA samples showed an increased concentration of putrescine and spermidine vs. TAV and donor samples, together with a decreased mRNA level of polyamine anabolic enzymes and of the putative polyamine transporter SLC7A1/CAT-1. The catabolic enzyme spermidine/spermine N1-acetyltransferase 1 showed a significant mRNA increase in TAV samples only, together with a decreased concentration of spermine. The decreased expression of SLC7A1/CAT-1 and ODC1 mRNAs in BAV corresponded to increased or unchanged expression of the respective proteins. ODC was located mainly in smooth muscle cell (SMC) nucleus in TAV and donor samples, while it was present also in SMC cytoplasm in BAV samples, suggesting its activation. In conclusion, BAV, but not TAV non-dilated samples show increased polyamine concentration, accompanied by the activation of a regulatory negative feedback mechanism.
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| 6. |
- Jekell, A, et al.
(författare)
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The interrelation of endothelial function and microvascular reactivity in different vascular beds, and risk assessment in hypertension: results from the Doxazosin-ramipril study
- 2019
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Ingår i: Heart and vessels. - : Springer Science and Business Media LLC. - 1615-2573 .- 0910-8327. ; 34:3, s. 484-495
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Tidskriftsartikel (refereegranskat)abstract
- There are several non-invasive methods to study endothelial function, but their interrelation and association to cardiovascular risk have not been well evaluated. We studied macrovascular and microvascular endothelial function simultaneously in different vascular beds in relation to cardiovascular mortality risk (Systematic Coronary Risk Evaluation, SCORE) and hypertension induced cardiac organ damage, and their interrelationship. The study investigated 71 hypertensive patients by forearm post-ischemic flow-mediated vasodilation, pulse wave analysis (applanation tonometry) and beta 2-adrenoceptor agonist stimulation for changes in reflection index, skin microvascular reactivity by laser Doppler fluxmetry with iontophoresis and heat-induced hyperaemia, and coronary microvascular function by subendocardial viability ratio (derived from pulse wave analysis). Flow mediated vasodilation related inversely to SCORE (r = 0.34, P = 0.011). Adding microalbuminuria and pulse wave velocity strengthened the associations. Pulse wave reflection changes did not relate to SCORE. Skin microvascular reactivity related inversely to SCORE (peak flux change to sodium nitroprusside r = 0.29, P = 0.033, and to heating r = 0.31, P = 0.018). Subendocardial viability ratio did not relate to SCORE. Endothelial function indices showed no consistent relation to cardiac target organ damage. The agreement between the different methods for evaluating indices of macrovascular and microvascular endothelial function was weak. In conclusion, indices of macrovascular and microvascular endothelial function relate to cardiovascular mortality risk. Their use may improve cardiovascular risk prediction in hypertension. However, methods representing different vascular beds show little interrelationship and are not interchangeable, which may depend on different pathogenetic mechanisms representing different aspects of future cardiovascular risk.Trial registry: NCT02901977
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| 7. |
- Nyström, Thomas, et al.
(författare)
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Estimated glucose disposal rate and long-term survival in type 2 diabetes after coronary artery bypass grafting.
- 2017
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Ingår i: Heart and vessels. - : Springer Science and Business Media LLC. - 1615-2573 .- 0910-8327. ; 32:3, s. 269-278
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Tidskriftsartikel (refereegranskat)abstract
- We performed a nationwide population-based cohort study to investigate the association between estimated glucose disposal rate (eGDR) and long-term survival after coronary artery bypass grafting (CABG) in patients with type 2 diabetes. All patients who underwent primary CABG in Sweden from 2006 to 2013 were identified from the SWEDEHEART register and by record linkage to the National Diabetes Register; all patients with type 2 diabetes were included and formed the study population. Patients were followed until 2013 through national registers for major adverse cardiovascular events and death from any cause. eGDR was calculated using waist circumference, hemoglobin A1c, and presence or the absence of hypertension. The association between eGDR and death was estimated using multivariable Cox regression. A total of 3256 patients were included. During a mean follow-up of 3.1years (10,227 person-years), in total, 14% patients died: 17% (n=186) in the 1st tertile (lowest eGDR), 14% (n=145) in the 2nd tertile, and 13% (n=133) in the 3rd tertile (highest eGDR). There was a significant association between eGDR and increased risk of death: adjusted hazard ratio (95% confidence interval): 1.46 (1.12-1.90) for the 1st eGDR tertile compared to the 3rd and highest eGDR tertile. In conclusion, patients with type 2 diabetes who underwent CABG, a low eGDR, were associated with an increased risk of long-term all-cause mortality that was independent of other cardiovascular and metabolic risk factors. Insulin resistance measured by eGDR could be a useful risk marker in patients with type 2 diabetes and ischemic heart disease.
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| 8. |
- Sandqvist, Anna, et al.
(författare)
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Plasma l-arginine levels distinguish pulmonary arterial hypertension from left ventricular systolic dysfunction
- 2018
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Ingår i: Heart and Vessels. - : Springer. - 0910-8327 .- 1615-2573. ; 33:3, s. 255-263
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Tidskriftsartikel (refereegranskat)abstract
- Pulmonary arterial hypertension (PAH) is a life-threatening condition, characterized by an imbalance of vasoactive substances and remodeling of pulmonary vasculature. Nitric oxide, formed from l-arginine, is essential for homeostasis and smooth muscle cell relaxation in PAH. Our aim was to compare plasma concentrations of l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) in PAH compared to left ventricular systolic dysfunction (LVSD) and healthy subjects. This was an observational, multicenter study comparing 21 patients with PAH to 14 patients with LVSD and 27 healthy subjects. Physical examinations were obtained and blood samples were collected. Plasma levels of ADMA, SDMA, l-arginine, l-ornithine, and l-citrulline were analyzed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Plasma levels of ADMA and SDMA were higher, whereas l-arginine and l-arginine/ADMA ratio were lower in PAH patients compared to healthy subjects (p < 0.001). Patients with PAH also had lower levels of l-arginine than patients with LVSD (p < 0.05). l-Arginine correlated to 6 min walking distance (6MWD) (r s = 0.58, p = 0.006) and l-arginine/ADMA correlated to WHO functional class (r s = −0.46, p = 0.043) in PAH. In conclusion, l-arginine levels were significantly lower in treatment naïve PAH patients compared to patients with LVSD. Furthermore, l-arginine correlated with 6MWD in PAH. l-arginine may provide useful information in differentiating PAH from LVSD.
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