14
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Oscillatory fluid-induced mechanobiology in heart valves with parallels to the vasculature

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Forces generated by blood flow are known to contribute to cardiovascular development and remodeling. These hemodynamic forces induce molecular signals that are communicated from the endothelium to various cell types. The cardiovascular system consists of the heart and the vasculature, and together they deliver nutrients throughout the body. While heart valves and blood vessels experience different environmental forces and differ in morphology as well as cell types, they both can undergo pathological remodeling and become susceptible to calcification. In addition, while the plaque morphology is similar in valvular and vascular diseases, therapeutic targets available for the latter condition are not effective in the management of heart valve calcification. Therefore, research in valvular and vascular pathologies and treatments have largely remained independent. Nonetheless, understanding the similarities and differences in development, calcific/fibrous pathologies and healthy remodeling events between the valvular and vascular systems can help us better identify future treatments for both types of tissues, particularly for heart valve pathologies which have been understudied in comparison to arterial diseases.

          Related collections

          Most cited references98

          • Record: found
          • Abstract: found
          • Article: not found

          Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques.

          Dysregulated extracellular matrix (ECM) metabolism may contribute to vascular remodeling during the development and complication of human atherosclerotic lesions. We investigated the expression of matrix metalloproteinases (MMPs), a family of enzymes that degrade ECM components in human atherosclerotic plaques (n = 30) and in uninvolved arterial specimens (n = 11). We studied members of all three MMP classes (interstitial collagenase, MMP-1; gelatinases, MMP-2 and MMP-9; and stromelysin, MMP-3) and their endogenous inhibitors (TIMPs 1 and 2) by immunocytochemistry, zymography, and immunoprecipitation. Normal arteries stained uniformly for 72-kD gelatinase and TIMPs. In contrast, plaques' shoulders and regions of foam cell accumulation displayed locally increased expression of 92-kD gelatinase, stromelysin, and interstitial collagenase. However, the mere presence of MMP does not establish their catalytic capacity, as the zymogens lack activity, and TIMPs may block activated MMPs. All plaque extracts contained activated forms of gelatinases determined zymographically and by degradation of 3H-collagen type IV. To test directly whether atheromata actually contain active matrix-degrading enzymes in situ, we devised a method which allows the detection and microscopic localization of MMP enzymatic activity directly in tissue sections. In situ zymography revealed gelatinolytic and caseinolytic activity in frozen sections of atherosclerotic but not of uninvolved arterial tissues. The MMP inhibitors, EDTA and 1,10-phenanthroline, as well as recombinant TIMP-1, reduced these activities which colocalized with regions of increased immunoreactive MMP expression, i.e., the shoulders, core, and microvasculature of the plaques. Focal overexpression of activated MMP may promote destabilization and complication of atherosclerotic plaques and provide novel targets for therapeutic intervention.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Partial carotid ligation is a model of acutely induced disturbed flow, leading to rapid endothelial dysfunction and atherosclerosis.

            Atherosclerosis is closely associated with disturbed flow characterized by low and oscillatory shear stress, but studies directly linking disturbed flow to atherogenesis is lacking. The major reason for this has been a lack of an animal model in which disturbed flow can be acutely induced and cause atherosclerosis. Here, we characterize partial carotid ligation as a model of disturbed flow with characteristics of low and oscillatory wall shear stress. We also describe a method of isolating intimal RNA in sufficient quantity from mouse carotid arteries. Using this model and method, we found that partial ligation causes upregulation of proatherogenic genes, downregulation of antiatherogenic genes, endothelial dysfunction, and rapid atherosclerosis in 2 wk in a p47(phox)-dependent manner and advanced lesions by 4 wk. We found that partial ligation results in endothelial dysfunction, rapid atherosclerosis, and advanced lesion development in a physiologically relevant model of disturbed flow. It also allows for easy and rapid intimal RNA isolation. This novel model and method could be used for genome-wide studies to determine molecular mechanisms underlying flow-dependent regulation of vascular biology and diseases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The emerging role of valve interstitial cell phenotypes in regulating heart valve pathobiology.

              The study of the cellular and molecular pathogenesis of heart valve disease is an emerging area of research made possible by the availability of cultures of valve interstitial cells (VICs) and valve endothelial cells (VECs) and by the design and use of in vitro and in vivo experimental systems that model elements of valve biological and pathobiological activity. VICs are the most common cells in the valve and are distinct from other mesenchymal cell types in other organs. We present a conceptual approach to the investigation of VICs by focusing on VIC phenotype-function relationships. Our review suggests that there are five identifiable phenotypes of VICs that define the current understanding of their cellular and molecular functions. These include embryonic progenitor endothelial/mesenchymal cells, quiescent VICs (qVICs), activated VICs (aVICs), progenitor VICs (pVICs), and osteoblastic VICs (obVICs). Although these may exhibit plasticity and may convert from one form to another, compartmentalizing VIC function into distinct phenotypes is useful in bringing clarity to our understanding of VIC pathobiology. We present a conceptual model that is useful in the design and interpretation of studies on the function of an important phenotype in disease, the activated VIC. We hope this review will inspire members of the investigative pathology community to consider valve pathobiology as an exciting new frontier exploring pathogenesis and discovering new therapeutic targets in cardiovascular diseases.
                Bookmark

                Author and article information

                Journal
                Vasc Biol
                Vasc Biol
                vb
                Vascular Biology
                Bioscientifica Ltd (Bristol )
                2516-5658
                2020
                17 February 2020
                : 2
                : 1
                : R59-R71
                Affiliations
                [1 ]Engineering Center , Department of Biomedical Engineering, Florida International University, Miami, Florida, USA
                Author notes
                Correspondence should be addressed to S Ramaswamy: sramaswa@ 123456fiu.edu
                Author information
                http://orcid.org/0000-0003-4108-7141
                Article
                VB-19-0031
                10.1530/VB-19-0031
                7439923
                32923975
                9e7f5d4f-6293-45b4-a7c2-7c0d42200774
                © 2020 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 07 January 2020
                : 17 February 2020
                Categories
                Review

                oscillatory,shear stress,valvular,calcific,remodeling
                oscillatory, shear stress, valvular, calcific, remodeling

                Comments

                Comment on this article