Vascular Smooth Muscle Growth: Autocrine Growth Mechanisms

Abstract

Vascular smooth muscle cells (VSMC) exhibit several growth responses to agonists that regulate their function including proliferation (hyperplasia with an increase in cell number), hypertrophy (an increase in cell size without change in DNA content), endoreduplication (an increase in DNA content and usually size), and apoptosis. Both autocrine growth mechanisms (in which the individual cell synthesizes and/or secretes a substance that stimulates that same cell type to undergo a growth response) and paracrine growth mechanisms (in which the individual cells responding to the growth factor synthesize and/or secrete a substance that stimulates neighboring cells of another cell type) are important in VSMC growth. In this review I discuss the autocrine and paracrine growth factors important for VSMC growth in culture and in vessels. Four mechanisms by which individual agonists signal are described: direct effects of agonists on their receptors, transactivation of tyrosine kinase-coupled receptors, generation of reactive oxygen species, and induction/secretion of other growth and survival factors. Additional growth effects mediated by changes in cell matrix are discussed. The temporal and spatial coordination of these events are shown to modulate the environment in which other growth factors initiate cell cycle events. Finally, the heterogeneous nature of VSMC developmental origin provides another level of complexity in VSMC growth mechanisms.

Nuclear Factor of Activated T Cells c1 Mediates p21-activated Kinase 1 Activation in the Modulation of Chemokine-induced Human Aortic Smooth Muscle Cell F-actin Stress Fiber Formation, Migration, and Proliferation and Injury-induced Vascular Wall Remodeling

“…Vascular smooth muscle cell (VSMC) 3 migration to, and proliferation in, the intimal region are considered hallmarks of neointimal development following angioplasty and vein grafting (1,2). In recent years, many reports showed that besides resident VSMCs, progenitor cell recruitment to and homing at the site of vascular injury also plays a role in neointima formation, at least in rodent animal models (3,4).…”

“…Among the many theories put forth in explaining the abnormal multiplication of these cells, their dedifferentiation gained momentum (5,6). Although the exact cause for the switching of VSMCs from the contractile to the synthetic phenotype is currently unclear, a variety of molecules produced at the site of vascular injury appear to be involved in the modulation of their migration and proliferation (2,7). One such molecule is monocyte chemotactic protein 1 (MCP1) (8).…”

Cytosolic Phospholipase A2 Is an Effector of Jak/STAT Signaling and Is Involved in Platelet-derived Growth Factor BB-induced Growth in Vascular Smooth Muscle Cells

“…Indeed, increased levels of growth factors such as platelet-derived growth factor, eicosanoids such as hydroxyeicosatetraenoic acids, and oxidants such as oxidized low density lipoprotein have been reported in atheromatous arteries compared with normal arteries (3)(4)(5)(6)(7)(8)(9). As these molecules utilize divergent early mitogenic signaling events in the induction of VSMC growth (10,11), targeting inhibition of the activity of a single mitogen might not be able to suppress VSMC growth and lesion formation. However, identifying the mechanisms that are less redundant and that are involved in the mitogenic and chemotactic activities of many of these molecules may advance therapeutic developments that mitigate VSMC growth and vessel wall lesions.…”

Vein graft failure: current clinical practice and potential for gene therapeutics

“…This predominantly involves VSMC proliferation and deposition of ECM. 55,56 This process of vein graft remodelling also intrinsically alters intragraft haemodynamics. The growth of the graft is asymmetric that may also promote chaotic blood flow patterns, 57 resulting in enhanced platelet and leukocyte adhesion, and thrombosis that in turn can augment intimal thickening.…”