A 340 kDa hyaluronic acid secreted by human vascular smooth muscle cells regulates their proliferation and migration

摘要: 3To whom correspondence should be addressed The formation of atherosclerotic lesions is characterized by invasion vascular smooth muscle cells (VSMC) into the tunica intima arterial wall and subsequently increased proliferation VSMC, a process apparently restricted to intimal layer blood vessels. Both events are preceded pathological overexpression several growth factors, such as platelet-derived factor (PDGF) which potent mitogen for VSMC can induce their chemotaxis. PDGF generally not expressed in normal artery but it upregulated lesions. We have previously shown that PDGF-BB specifically stimulates proliferating secrete 340 kDa hyaluronic acid (HA-340). Here, we present evidence regarding biological functions this glycan. observed HA-340 inhibited PDGF-induced human dosedependent manner enhanced PDGF-dependent through basement membrane barrier. These effects were abolished following treatment with hyaluronidase. effect on coincided secretion 72-kDa type IV collagenase was completely blocked GM6001, hydroxamic inhibitor matrix metalloproteinases. did exert any chemotactic potency, nor affect chemotaxis along gradient. In atheromatic aortas, found negative concentration gradient from media plaque. Our findings suggest may linked pathogenesis atherosclerosis, modulating invasion.