Which of the following statements on smooth muscle cells is/are correct?

A. Smooth muscle cells can undergo pheotypic changes in response to injury.

B. Platelet-derived growth factor (PDGF) requires a progression factor to initiate smooth muscle cell growth.

C. NO can be produced by smooth muscle cells.

D. Changes in the composition of the extracellular matrix modulate smooth muscle cell growth.

E. Smooth muscle cells are the principal cell involved in the development of intimal hyperplasia.

DISCUSSION: Smooth muscle cells are the principal cells found in the media of a vessel. They are embedded in a matrix of connective tissue elements and provide mechanical and structural support to the vessel. In addition to their vasoreactive characteristics, smooth muscle cells are capable of synthesizing and secreting elements of the extracellular matrix, particularly proteoglycans. The exact mechanisms whereby smooth muscle cell proliferation is initiated, controlled, reduced, and eventually suppressed are not fully understood. Quiescent vascular smooth muscle cells are well-differentiated cells characterized by an abundance of contractile proteins, predominantly smooth muscle cell actin and myosin but little rough endoplasmic reticulum. Once activated, smooth muscle cells lose their differentiated state, acquire abundant endoplasmic reticulum, and commence the synthesis of extracellular matrix. After cytokine stimulation, smooth muscle cells synthesize iNOS and produce nanomoles of NO for at least 24 hours. Smooth muscle cell proliferation depends on the presence of PDGF, basic fibroblast growth factor (bFGF), and insulin-like growth factor 1 (IGF-1). IGF-1 acts as a progression factor for PDGF in smooth muscle cells, and both in vivo and in vitro there is synergism between these two growth promoters. Smooth muscle cell growth in the wall can be modulated by various extracellular matrix substances such as collagen (type V), several glycoproteins, and the glycosoaminoglycans. Both NO and prostacyclin inhibit cell proliferation. Intimal hyperplasia is a structural lesion that develops in injured blood vessels after injury and is the result of smooth muscle cell migration into and proliferation within the intima of a blood vessel.