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- Artiach, G, et al.
(författare)
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Proteoglycan 4 is Increased in Human Calcified Aortic Valves and Enhances Valvular Interstitial Cell Calcification
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Aortic valve stenosis (AVS), a consequence of increased fibrosis and calcification of the aortic valve leaflets, causes progressive narrowing of the aortic valve. Proteoglycans, structural components of the aortic valve, accumulate in regions with fibrosis and moderate calcification. Particularly, proteoglycan 4 (PRG4) has been identified in fibrotic parts of aortic valves. However, the role of PRG4 in the context of AVS and aortic valve calcification has not yet been determined. Here, transcriptomics, histology, and immunohistochemistry were performed in human aortic valves from patients undergoing aortic valve replacement. Human valve interstitial cells (VICs) were used for calcification experiments and RNA expression analysis. PRG4 was significantly upregulated in thickened and calcified regions of aortic valves compared with healthy regions. In addition, mRNA levels of PRG4 positively associated with mRNA for proteins involved in cardiovascular calcification. Treatment of VICs with recombinant human PRG4 enhanced phosphate-induced calcification and increased the mRNA expression of bone morphogenetic protein 2 and the runt-related transcription factor 2. In summary, PRG4 was upregulated in the development of AVS and promoted VIC osteogenic differentiation and calcification. These results suggest that an altered valve leaflet proteoglycan composition may play a role in the progression of AVS.
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- Dai, L, et al.
(författare)
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Aortic Valve Calcium Associates with All-Cause Mortality Independent of Coronary Artery Calcium and Inflammation in Patients with End-Stage Renal Disease
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Aortic valve calcium (AVC) and coronary artery calcium (CAC) are common complications in end-stage renal disease (ESRD). We investigated the prognostic significance of overlapping presence of AVC and CAC, and whether AVC was associated with all-cause mortality independent of the presence of CAC in ESRD. Methods: 259 ESRD patients (median age 55 years, 67% males) undergoing cardiac computed tomography were included. Framingham risk score (FRS), presence of cardiovascular disease (CVD), statin use, nutritional status and other relevant laboratory data were determined at baseline. During follow-up for median 36 months, 44 patients died, and 68 patients underwent renal transplantation. Results: The baseline overlap presence of AVC and CAC was 37%. Multivariate regression analysis showed that FRS (odds ratio (OR) 2.25; 95% confidence interval (95% CI), 1.43–3.55) and CAC score (OR (95% CI), 2.18 (1.34–3.59)) were independent determinants of AVC. In competing-risk regression models adjusted for presence of CAC, inflammation, nutritional status, CVD, FRS and statin use, AVC remained independently associated with all-cause mortality (sub-hazard ratio (95% CI), 2.57 (1.20–5.51)). Conclusions: The overlap of AVC and CAC was 37% in this ESRD cohort. AVC was associated with increased all-cause mortality independent of presence of CAC, traditional risk factors and inflammation.
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- Karadimou, G, et al.
(författare)
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TLR7 Expression Is Associated with M2 Macrophage Subset in Calcific Aortic Valve Stenosis
- 2020
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Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Calcific aortic valve stenosis (CAVS) is a common age-related disease characterized by active calcification of the leaflets of the aortic valve. How innate immune cells are involved in disease pathogenesis is not clear. In this study we investigate the role of the pattern recognition receptor Toll-like receptor 7 (TLR7) in CAVS, especially in relation to macrophage subtype. Human aortic valves were used for mRNA expression analysis, immunofluorescence staining, or ex vivo tissue assays. Response to TLR7 agonist in primary macrophages and valvular interstitial cells (VICs) were investigated in vitro. In the aortic valve, TLR7 correlated with M2 macrophage markers on mRNA levels. Expression was higher in the calcified part compared with the intermediate and healthy parts. TLR7+ cells were co-stained with M2-type macrophage receptors CD163 and CD206. Ex vivo stimulation of valve tissue with the TLR7 ligand imiquimod significantly increased secretion of IL-10, TNF-α, and GM-CSF. Primary macrophages responded to imiquimod with increased secretion of IL-10 while isolated VICs did not respond. In summary, in human aortic valves TLR7 expression is associated with M2 macrophages markers. Ex vivo tissue challenge with TLR7 ligand led to secretion of immunomodulatory cytokine IL-10. These results connect TLR7 activation in CAVS to reduced inflammation and improved clearance.
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- Plunde, O, et al.
(författare)
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Cardiovascular Risk Factors and Hemodynamic Measures as Determinants of Increased Arterial Stiffness Following Surgical Aortic Valve Replacement
- 2021
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Ingår i: Frontiers in cardiovascular medicine. - : Frontiers Media SA. - 2297-055X. ; 8, s. 754371-
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Tidskriftsartikel (refereegranskat)abstract
- Valvular and arterial function are tightly intertwined, both in terms of structural changes and hemodynamics. While proximal valvulo-vascular coupling contributes to the cardiovascular consequences of aortic stenosis, less is known on how peripheral arterial stiffness relates to aortic valve disease. Previous studies have shown conflicting results regarding the impact of aortic valve replacement on arterial stiffness. The aim of the present study was therefore to determine predictors of arterial stiffness in patients with and without aortic valve disease undergoing cardiac surgery. Cardio ankle vascular index (CAVI) and carotid femoral pulse wave velocity (cfPWV) were measured to determine arterial stiffness the day before and 3 days after surgery for either ascending aortic or aortic valve disease. Stratification on indication for surgery revealed that CAVI was significantly lower in patients with aortic valve stenosis (n = 45) and aortic valve regurgitation (n=30) compared with those with isolated ascending aortic dilatation (n = 13). After surgery, a significant increased CAVI was observed in aortic stenosis (median 1.34, IQR 0.74–2.26, p < 0.001) and regurgitation (median 1.04, IQR 0.01–1.49, p = 0.003) patients while cfPWV was not significantly changed. Age, diabetes, low body mass index, low pre-operative CAVI, as well as changes in ejection time were independently associated with increased CAVI after surgery. The results of the present study suggest aortic valve disease as cause of underestimation of arterial stiffness when including peripheral segments. We report cardiovascular risk factors and pinpoint the hemodynamic aspect ejection time to be associated with increased CAVI after aortic valve surgery.
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