The extracellular matrix can regulate vascular cell migration, proliferation, and survival: relationships to vascular disease

Abstract

The extracellular matrix (ECM) of the normal artery wall is a collection of fibrous proteins and associated glycoproteins embedded in a hydrated ground substance of glycosaminoglycans and proteoglycans. These distinct molecules are organized into a highly ordered network that are closely associated with the vascular cells that produce them. In addition to providing the architectural framework for the artery wall that imparts mechanical support and viscoelasticity, the ECM can regulate the behaviour of vascular cells, including their ability to migrate, proliferate and survive injury. The composition of the ECM is different within intimal lesions of atherosclerosis, which are composed of monocytes and lymphocytes from the circulation and smooth muscle cells (SMC) that migrate from the media to the intima (Ross 1993, 1999), and these differences may contribute to the altered phenotype of vascular cells within lesions. This review will briefly outline the ECM changes observed in atherosclerosis and restenosis and the potential relationship of these changes to altered vascular cell functions.

Figure 1

A transmission electron micrograph of a developing monkey aorta. Within normal vessels, smooth muscle layers are embedded in a matrix composed of elastic elements, collagen and proteoglycans. Two endothelial cells can be seen at the lumen (although their nuclei are not apparent in this thin section). Beneath the endothelial cells are newly forming elastic fibres (E) that are separated from the endothelium by basement membrane and collagen fibrils. A layer of smooth muscle lies beneath the forming elastic fibres, which is separated from another layer of smooth muscle by well-formed elastic laminae (EL). Reprinted with permission from Ross R. (1988) In Heart Disease:A Textbook of Cardiovascular Medicine, 3rd edition. (Ed. E. Braunwald) Philadelphia: W.B. Saunders Co., 1135–1152.

Figure 2

Smooth muscle cells within atherosclerotic lesions have abundant rough endoplasmic reticula. A transmission electron micrograph of a deep layer of a fatty streak in the thoracic aorta of a nonhuman primate six months after initiation of a high cholesterol diet. The extracellular space between the smooth muscle cells in the deep layer of the fatty streak contains collagen, elastin and numerous extracellular liposomes. The smooth muscle cells have abundant rough endoplasmic reticula and few myofilaments. Reprinted with permission from Masuda J. & Ross R. (1990) Arteriosclerosis10, 164–177.