"Obese" smooth muscle cells fail to assemble collagen fibrils.

Smooth muscle cells (SMCs) play an important role in the stabilization of atherosclerotic plaques. They contribute to form a firm fibrous cap by synthesizing and assembling fibrillar collagen I, a process that requires the synthesis of fibronectin and activation of integrins. However, extracellular matrix composition changes during the formation of atherosclerotic plaques. Type I and III collagens predominate in the healthy vessel wall, whereas during atherogenesis, fibronectin and type VIII collagen are synthesized by vascular SMCs.1 In advanced plaques, SMCs and macrophages synthesize matrix metalloproteinases which degrade matrix proteins, thereby weakening the fibrous cap. During lesion development, SMC phenotypes change from a “contractile” to a “synthetic” phenotype.2 It has been shown that inflammatory mediators and oxidized phospholipids induce phenotypic switching in SMCs and consequently also modulate matrix metalloproteinases and collagen production.3 The SMC phenotype that determines migration and proliferation also controls matrix synthesis and degradation.4 Monomeric type I collagen, a byproduct of collagen I breakdown, has been shown to further potentiate an inflammatory SMC phenotype,5 possibly exacerbating the process of collagen turnover. Moreover, induction of apoptosis in SMCs results in decreased cellularity and thus enhanced vulnerability of atherosclerotic plaques. In summary, imbalance toward decreased production and assembly and increased degradation of matrix proteins such as collagens and fibronectin is believed to result in thinning and thus destabilization of the atherosclerotic fibrous cap.6