Interstitial cells of the heart valves possess characteristics similar to smooth muscle cells.

Abstract

Interstitial cells of heart atrioventricular and sigmoid valves were examined in several laboratory animals (rabbit, hamster, rat, and mouse) and in humans. These cells constitute a large fraction of the total cell population of the valve; in mouse atrioventricular valves, they amount to approximately 30% of the volumetric density. By their ultrastructural features and functional properties, valvular interstitial cells are intermediate between fibroblasts and vascular smooth muscle cells. Like fibroblasts, valvular interstitial cells lack a basal lamina establishing direct and extensive contacts with collagen fibers, elastin microfibrils, and proteoglycans of the matrix. The cells have numerous slender and long processes, connected to one another, forming a complex cellular framework spanning the entire valve. Similar to smooth muscle cells, valvular interstitial cells are extensively coupled by communicating junctions as shown by thin sections, freeze-fracture, lanthanum staining, and carboxyfluorescein microinjection. The cells contain numerous bundles of actin filaments, which are decorated by the S1 fragment of heavy meromyosin. Valvular interstitial cells also express cyclic guanosine-monophosphate-dependent protein kinase, as detected by immunofluorescence and immunoperoxidase histochemistry. Motor nerve endings are located closely apposed to valvular interstitial cells: structurally most of them appear to be of the adrenergic type. Valvular interstitial cells contract on epinephrine or angiotensin II stimulation as shown both in culture and in situ (valvular strips). Taken together these observations suggest that VIC may have contractile properties, which can account for a controlled tonus, actively correlated with the cyclically changing forces acting on valves during diastole and systole.

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).…”

“…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). They come in close contact with extracellular collagen and may be targets for nearby adrenergic motor nerves, the terminals of which are closely apposed (30 -80 nm) (13,26).…”

“…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.…”

The epicardium and epicardially derived cells (EPDCs) as cardiac stem cells

“…The EPDCs located in the AV cushions are also WT1/ RALDH2-negative and express caldesmon, a smooth muscle marker that is also expressed in CoSMCs from EPDC origin. Although there are no true SMCs in the adult vertebrate AV valves, around 10% of the cells in the valves have been reported to show an intermediate phenotype between fibroblasts and vascular SMCs (Filip et al, 1986). Inhibition of normal epicardial development resulted in a series of cardiac defects, including abnormalities in the AV valve apparatus (Pérez-Pomares et al, 2002b).…”

Transforming Growth Factor-β Regulates the Growth of Valve Interstitial Cells in Vitro

“…[3][4][5] They are situated underneath the surface endocardium 1 and embedded in an extracellular matrix (ECM) that they secrete and actively remodel. 5 VICs are the master cells within the valve because they regulate both physiological and pathological processes.…”