Dataset Information

Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair.

ABSTRACT: Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level in vivo state and in vitro-based mechanobiology studies has yet to be made. We thus developed an integrated experimental-computational approach to elucidate MV tissue and interstitial cell responses to varying tissue strain levels. Comprehensive results at different length scales revealed that normal responses are observed only within a defined range of tissue deformations, whereas deformations outside of this range lead to hypo- and hyper-synthetic responses, evidenced by changes in ?-smooth muscle actin, type I collagen, and other ECM and cell adhesion molecule regulation. We identified MV interstitial cell deformation as a key player in leaflet tissue homeostatic regulation and, as such, used it as the metric that makes the critical link between in vitro responses to simulated equivalent in vivo behaviour. Results indicated that cell responses have a delimited range of in vivo deformations that maintain a homeostatic response, suggesting that deviations from this range may lead to deleterious tissue remodelling and failure.

SUBMITTER: Ayoub S

PROVIDER: S-EPMC5665836 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair.

Ayoub Salma S Lee Chung-Hao CH Driesbaugh Kathryn H KH Anselmo Wanda W Hughes Connor T CT Ferrari Giovanni G Gorman Robert C RC Gorman Joseph H JH Sacks Michael S MS

Journal of the Royal Society, Interface 20171001 135

Mechanical stress is one of the major aetiological factors underlying soft-tissue remodelling, especially for the mitral valve (MV). It has been hypothesized that altered MV tissue stress states lead to deviations from cellular homeostasis, resulting in subsequent cellular activation and extracellular matrix (ECM) remodelling. However, a quantitative link between alterations in the organ-level <i>in vivo</i> state and <i>in vitro-</i>based mechanobiology studies has yet to be made. We thus devel ...[more]

PMID: 29046338

Similar Datasets

Project description:BackgroundSurgical left atrial appendage occlusion (SLAAO) may be associated with a lower risk of thromboembolism in patients with atrial fibrillation undergoing cardiac surgery. However, evidence regarding the effectiveness of SLAAO in patients undergoing mechanical heart valve replacement (MHVR) is lacking. Therefore, we aimed to evaluate the association between SLAAO and the cardiovascular outcomes in patients with atrial fibrillation undergoing MHVR.MethodsWe retrospectively analyzed data for 497 patients with atrial fibrillation; 27.6% of the patients underwent SLAAO, and the remainder of the patients did not (No-SLAAO group). The primary outcome was a composite of ischemic stroke, systemic embolism, and all-cause mortality. Cumulative event-free survival rates were estimated using Kaplan-Meier curves, and we performed multivariate Cox analyses to evaluate the association between SLAAO and outcomes. We used one-to-one propensity score matching to balance patients' baseline characteristics, and analyzed 120 matching pairs.ResultsFive patients died within 30 days postoperatively, and there were no significant differences between the two groups regarding in-hospital complications (all P > 0.05). After a median follow-up of 14 months, 14 primary events occurred. Kaplan-Meier curves showed no difference in the cumulative incidence of freedom from the primary outcome (log-rank P = 0.830), hemorrhagic events (log-rank P = 0.870), and the secondary outcome (log-rank P = 0.730), between the two groups. Multivariable Cox proportional hazards regression analysis showed no association between SLAAO and any outcome (all P > 0.05). After propensity score matching, cardiopulmonary bypass time and aortic cross-clamp time, and the postoperative length of stay were significantly longer in the SLAAO group (all P < 0.05); results were similar to the unadjusted analyses.ConclusionsConcomitant SLAAO and MHVR was associated with longer length of stay, and cardiopulmonary bypass time and aortic cross-clamp time, but was not associated with additional protective effects against thromboembolic events and mortality during the 14-month follow-up.

Project description:BackgroundThe clinical outcome of mitral valve repair (MVP) is considerably more favorable than that of mitral valve replacement (MVR) in patients with degenerative mitral disease. However, rheumatic heart disease (RHD) is still the predominant cause of mitral valve surgery in developing countries and the advantages of MVP in RHD have still not been definitely proven. The aim of this meta-analysis was thus to evaluate the suitability of MVP in patients with RHD. Considering the difference between mechanical and biological valves, we distinguished them from each other and compared them with MVP individually.MethodsA comparison of clinical outcomes of MVP and MVR in patients with RHD was performed based on clinical trial data. Relevant articles published from January 1, 1990 until March 1, 2020 were identified in Pubmed, Cochrane Library, and China National Knowledge Infrastructure database (CNKI). Studies that lacked direct comparisons between MVP and MVR were excluded.ResultsA total of 16 studies with 8659 patients were included in the analysis. The MVP group displayed lower early and long-term mortality, and fewer valve-related events and major adverse events. However, this patient group required more reoperations compared with the MVR group. Similar results were observed after distinguishing between mechanical and bioprosthetic valves to compare MVP with MVR (mech-valves), but no statistically significant difference was identified in the reoperation rate between MVP and MVR (bio-valves). MVP was further associated with increased risk of mitral reoperation in patients undergoing concomitant aortic valve replacement (AVR) surgery but without any improved early and long-term survival.ConclusionsMVP and MVR are beneficial for patients with RHD. For skilled surgeons, MVP can be performed for some suitable patients with RHD and is preferred for elderly patients or patients with contraindications of anticoagulation. However, MVR is more appropriate when concomitant AVR is needed.

Project description:Background: Aortic valve calcification is an active proliferative process, where interstitial cells of the valve transform into either myofibroblasts or osteoblast-like cells causing valve deformation, thickening of cusps and finally stenosis. This process may be triggered by several factors including inflammation, mechanical stress or interaction of cells with certain components of extracellular matrix. The matrix is different on the two sides of the valve leaflets. We hypothesize that inflammation and mechanical stress stimulate osteogenic differentiation of human aortic valve interstitial cells (VICs) and this may depend on the side of the leaflet. Methods: Interstitial cells isolated from healthy and calcified human aortic valves were cultured on collagen or elastin coated plates with flexible bottoms, simulating the matrix on the aortic and ventricular side of the valve leaflets, respectively. The cells were subjected to 10% stretch at 1 Hz (FlexCell bioreactor) or treated with 0.1 μg/ml lipopolysaccharide, or both during 24 h. Gene expression of myofibroblast- and osteoblast-specific genes was analyzed by qPCR. VICs cultured in presence of osteogenic medium together with lipopolysaccharide, 10% stretch or both for 14 days were stained for calcification using Alizarin Red. Results: Treatment with lipopolysaccharide increased expression of osteogenic gene bone morphogenetic protein 2 (BMP2) (5-fold increase from control; p = 0.02) and decreased expression of mRNA of myofibroblastic markers: α-smooth muscle actin (ACTA2) (50% reduction from control; p = 0.0006) and calponin (CNN1) (80% reduction from control; p = 0.0001) when cells from calcified valves were cultured on collagen, but not on elastin. Mechanical stretch of VICs cultured on collagen augmented the effect of lipopolysaccharide. Expression of periostin (POSTN) was inhibited in cells from calcified donors after treatment with lipopolysaccharide on collagen (70% reduction from control, p = 0.001), but not on elastin. Lipopolysaccharide and stretch both enhanced the pro-calcific effect of osteogenic medium, further increasing the effect when combined for cells cultured on collagen, but not on elastin. Conclusion: Inflammation and mechanical stress trigger expression of osteogenic genes in VICs in a side-specific manner, while inhibiting the myofibroblastic pathway. Stretch and lipopolysaccharide synergistically increase calcification.

Dataset Information

Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair.

Publications

Regulation of valve interstitial cell homeostasis by mechanical deformation: implications for heart valve disease and surgical repair.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets