Kevin M Bardon1, Mahdi Garelnabi2. 1. Department of Biomedical and Nutritional Sciences, Center for Population Health, University of Massachusetts, Lowell, MA. 2. Department of Biomedical and Nutritional Sciences, Center for Population Health, University of Massachusetts, Lowell, MA; Center for Population Health, University of Massachusetts, Lowell, MA, USA. Electronic address: Mahdi_Garelnabi@uml.edu.
Abstract
Calcific aortic valve disease (CAVD) is the most prevalent valvulopathy worldwide. Until recently, CAVD was viewed as a passive, degenerative process and an inevitable consequence of aging. Recent improvements in disease modeling, imaging, and analysis have greatly enhanced our understanding of CAVD. The aortic valve and its constituent cells are subjected to extreme changes in mechanical forces, so it follows that any changes in the underlying mechanobiology of the valve and its cells would have dire effects on function. Further, the mechanobiology of the aortic valve is intimately intertwined with numerous molecular pathways, with signal transduction between these aspects afforded by the dynamic plasma membrane. Changes to the plasma membrane itself, its regulation of the extracellular matrix, or the relay of signals into or out of the cell would negatively impact cell and tissue function. PURPOSE OF REVIEW: This review seeks to detail past and current published reports related to the mechanobiology of the aortic valve with a special emphasis on the implications of altered mechanobiology in the context of calcific aortic valve disease. RECENT FINDINGS: Investigations characterizing membrane composition and dynamics have provided new insights into the earliest stages of calcific aortic valve disease. Recent studies have suggested that the activation or suppression of key pathways contribute to disease progression but may also offer therapeutic targets. SUMMARY: This review highlights the critical involvement of mechanobiology and membrane dynamics in normal aortic valve physiology as well as valve pathology.
Calcific aortic valve disease (CAVD) is the most prevalent valvulopathy worldwide. Until recently, CAVD was viewed as a passive, degenerative process and an inevitable consequence of aging. Recent improvements in disease modeling, imaging, and analysis have greatly enhanced our understanding of CAVD. The aortic valve and its constituent cells are subjected to extreme changes in mechanical forces, so it follows that any changes in the underlying mechanobiology of the valve and its cells would have dire effects on function. Further, the mechanobiology of the aortic valve is intimately intertwined with numerous molecular pathways, with signal transduction between these aspects afforded by the dynamic plasma membrane. Changes to the plasma membrane itself, its regulation of the extracellular matrix, or the relay of signals into or out of the cell would negatively impact cell and tissue function. PURPOSE OF REVIEW: This review seeks to detail past and current published reports related to the mechanobiology of the aortic valve with a special emphasis on the implications of altered mechanobiology in the context of calcific aortic valve disease. RECENT FINDINGS: Investigations characterizing membrane composition and dynamics have provided new insights into the earliest stages of calcific aortic valve disease. Recent studies have suggested that the activation or suppression of key pathways contribute to disease progression but may also offer therapeutic targets. SUMMARY: This review highlights the critical involvement of mechanobiology and membrane dynamics in normal aortic valve physiology as well as valve pathology.
Authors: Zhongli Chen; Ying Shen; Qiqi Xue; Bo Wen Lin; Xiao Yan He; Yi Bo Zhang; Ying Yang; Wei Feng Shen; Ye Hong Liu; Ke Yang Journal: Front Cardiovasc Med Date: 2020-10-14