Molecular and functional characteristics of heart-valve interstitial cells

Abstract

The cells that reside within valve cusps play an integral role in the durability and function of heart valves. There are principally two types of cells found in cusp tissue: the endothelial cells that cover the surface of the cusps and the interstitial cells (ICs) that form a network within the extracellular matrix (ECM) within the body of the cusp. Both cell types exhibit unique functions that are unlike those of other endothelial and ICs found throughout the body. The valve ICs express a complex pattern of cell-surface, cytoskeletal and muscle proteins. They are able to bind to, and communicate with, each other and the ECM. The endothelial cells on the outflow and inflow surfaces of the valve differ from one another. Their individual characteristics and functions reflect the fact that they are exposed to separate patterns of flow and pressure. In addition to providing a structural role in the valve, it is now known that the biological function of valve cells is important in maintaining the integrity of the cusps and the optimum function of the valve. In response to inappropriate stimuli, valve interstitial and endothelial cells may also participate in processes that lead to valve degeneration and calcification. Understanding the complex biology of valve interstitial and endothelial cells is an important requirement in elucidating the mechanisms that regulate valve function in health and disease, as well as setting a benchmark for the function of cells that may be used to tissue engineer a heart valve.

Active stiffening of mitral valve leaflets in the beating heart

“…Anterior MV leaflets also contain VICs, occupying large portions of the leaflet, particularly the medial and distal regions (4,13,18,23,38,40). VICs have characteristics intermediate between fibroblasts and smooth muscle cells (13).…”

“…Medical and surgical therapies for this disease have traditionally assumed that the valve leaflets, the key components of the valve, are passive flaps (46). However, muscle fibers (2, 6, 11, 12, 18, 25, 30 -32, 34, 39, 41, 47, 48), blood vessels (6,8,11,24,26,37,39), and nerves (1, 6 -13, 18 -20, 26, 29, 35, 36, 39, 43-45) have been recognized in the MV leaflets of animals and humans since the 19th century, and the physiological function of these entities, along with other contractile elements in the leaflets, such as smooth muscle (8,18,26,47) and valvular interstitial cells (VICs) (4,13,18,23,26,28,38,40), is not understood.…”

On the multiscale modeling of heart valve biomechanics in health and disease

“…ICs are distributed throughout, and are responsible for maintaining, the leaflet tissue matrix and modulating disease pathology (Liu et al 2007). In the valve, ICs display a number of different phenotypes at different locations, and share some characteristics with fibroblasts and some with skeletal, cardiac, and smooth muscle cells (Roy et al 2000;Taylor et al 2003;Merryman et al 2006a;Chester and Taylor 2007). ICs are known to remodel over the human lifetime (Rabkin-Aikawa et al 2004), respond to physical deformations (Gupta et al 2008), and engage in signaling with other ICs and the extracellular matrix (Chester and Taylor 2007).…”

“…In the valve, ICs display a number of different phenotypes at different locations, and share some characteristics with fibroblasts and some with skeletal, cardiac, and smooth muscle cells (Roy et al 2000;Taylor et al 2003;Merryman et al 2006a;Chester and Taylor 2007). ICs are known to remodel over the human lifetime (Rabkin-Aikawa et al 2004), respond to physical deformations (Gupta et al 2008), and engage in signaling with other ICs and the extracellular matrix (Chester and Taylor 2007). On the other hand, ECs coat all of the blood-facing surfaces and have spatially varying phenotypes (Simmons et al 2005), respond to mechanical stimuli (Weinberg et al 2010), regulate valve pathologies (Butcher and Nerem 2007), and engage in signaling (Butcher and Nerem 2007).…”

Comparison of Mesenchymal Stem Cell Source Differentiation Toward Human Pediatric Aortic Valve Interstitial Cells within 3D Engineered Matrices

“…53,54 The 3D hybrid hydrogels in this study maintained fibroblastic-like phenotypes of pHAVIC without spontaneous osteogenic and adipogenic differentiation and with limited activation in HGM. However, both human ADMSC and BMMSC spontaneously expressed early marker (ALP) of osteogenic differentiation within the 3D hybrid hydrogels.…”