Vascular Smooth Muscle Cell Migration: Current Research and Clinical Implications

Abstract

Atherosclerosis and intimal hyperplasia are major causes of morbidity and mortality. These processes develop secondary to endothelial injury due to multiple stimuli, including smoking, diabetes mellitus, hypertension, and hyperlipidemia. Once this injury occurs, an essential element in the development of both these processes is vascular smooth muscle cell (VSMC) migration. Understanding the mechanisms involved in VSMC migration and ultimately the development of strategies by which this process can be inhibited, has been a major focus of research. The authors present a review of the extracellular proteins (growth factors, extracellular matrix components, and cell surface receptors) and intracellular signaling pathways involved in VSMC migration, as well as potential therapeutic approaches to inhibit this process.

βig-h3 triggers signaling pathways mediating adhesion and migration of vascular smooth muscle cells through αvβ5 integrin

“…These Fas-1 domain-containing proteins thus seem to play a common role in cell adhesion and migration. In addition to Fas-1 domain-containing family of proteins, some matrix proteins including collagen, fibronectin, thrombospondin-1, vitronectin, tenascin, and osteopontin have been shown to be elevated in response to vascular injury or in atherosclerotic plaues and promote migration of VSMCs (Giachelli et al, 1993;Liaw et al, 1994;Batchelor et al, 1998;Willis et al, 2004). In fact, osteopontin transgenic mice develop atherosclerosis (Chiba et al, 2002).…”

“…Given a key role of the αvβ5 integrin in VSMC migration on both βig-h3 and vitronectin that are elevated in atherosclerotic lesions, a function-blocking antibody against the αvβ5 integrin or a synthetic peptide containing the YH-18 motif could be a promising therapeutic approach against atherosclerosis. Some tyrosine kinases and small GTP-binding proteins have been known to play a role in VSMC migration that is induced by growth factors and extracellular matrix (Abedi and Zachary, 1995;Willis et al, 2004). Platelet-derived growth factor, a potent inducer of VSMC migration, stimulates the phosphorylation of PI3K, ERK, FAK, and paxillin (Abedi et al, 1995;Cospedal et al, 1999).…”

Endothelial and Vascular Smooth Cell Dysfunctions: A Comprehensive Appraisal

“…VSMCs have been determined to upregulate expression of receptor in response to vascular injury, inducing their chemotaxis; at the same time, these cells are able to increase the PDGF-AA, acting as a paracrine or autocrine regulator of their chemotaxis. This represents the first described autoregulation pathway of VSMCs on their own proliferation/migration (Willis et al, 2004). The second known requirement for cell cycle progression is availability of insulin-like growth factor (IGF-1), a co-factor that VSMCs require for completion of the cell cycle following stimulation with PDGF (Clemmons, 1984).…”

“…In his "response-to injury" hypothesis, Ross proposed that VSMCs in the wall normally exist in a quiescent state, but, when the endothelium is injured, platelets release factors that stimulate VSMCs movement into and replication within the arterial intima (Ross, 1981(Ross, -1982. Growth factors have been known to influence the differentiated state of VSMCs (Willis et al, 2004). An interesting possibility is that smooth muscle replication may be controlled by factors intrinsic to the vessel wall.…”

Cellular growth under hydrostatic pressure using bovine aortic EC-SMC co-cultured ePTFE vascular graft

“…Blood vessels are constantly subjected to stretch due to blood pressure and changes in stretch usually instigate adaptive alterations of vessel wall shape and composition, which is called vascular remodeling. The abnormal growth and proliferation of vascular smooth muscle cells (VSMC) as well as extracellular matrix (ECM) are considered to affect the process of vascular remodeling greatly (Lehoux and Tedgui, 1998;Willis et al, 2004), and such vascular remodeling is supposed to be related with pathogenesis of atherosclerosis.…”