The roles of salusins in atherosclerosis and related cardiovascular diseases

详细信息    查看全文

• 作者：Takuya Watanabe ; MD ; PhD^a ; ^{watanabe@toyaku.ac.jp} ; Kengo Sato ; PhD^a ; Fumiko Itoh ; PhD^a ; Yoshitaka Iso ; MD ; PhD^b ; Masaharu Nagashima ; MD ; PhD^c ; Tsutomu Hirano ; MD ; PhD^c ; Masayoshi Shichiri ; MD ; PhD^d
• 关键词：Salusins ; atherosclerosis ; macrophage ; vascular smooth muscle cell
• 刊名：Journal of the American Society of Hypertension
• 出版年：2011
• 出版时间：September-October 2011
• 年：2011
• 卷：5
• 期：5
• 页码：359-365
• 全文大小：386 K

文摘

Human salusin-¦Á and -¦Â are related peptides of 28 and 20 amino acids, respectively, produced from the same precursor, prosalusin. Salusin-¦Â exerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-¦Á. Human macrophage foam cell formation is significantly stimulated by salusin-¦Â, but suppressed by salusin-¦Á. Chronic salusin-¦Â infusion into apolipoprotein E¨Cknockout mice enhances atherosclerotic lesions, paralleling increases in foam cell formation and upregulation of scavenger receptors and of acyl-CoA:cholesterol acyltransferase-1 (ACAT1) in macrophages. In contrast, chronic salusin-¦Á infusion reduces atherosclerotic lesions accompanied by significant suppression of foam cell formation owing to ACAT1 downregulation. Salusin-¦Â is expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-¦Á and -¦Â immunoreactivity has been detected in human coronary atherosclerotic plaques, with dominance of salusin-¦Â in macrophage foam cells, VSMCs, and fibroblasts. Serum salusin-¦Á levels are markedly decreased in patients with angiographically proven coronary artery disease compared with patients with mild hypertension and healthy volunteers. Furthermore, among patients with acute coronary syndrome, serum salusin-¦Á levels are decreased in accordance with the severity of coronary atherosclerotic lesions. These findings suggest that salusin-¦Â may contribute to the pathogenesis of atherosclerosis. Decreased levels of salusin-¦Á in circulating blood and vascular tissue are closely linked?with human atherosclerosis. Therefore, salusin-¦Á could be a candidate biomarker for atherosclerosis and may be therapeutically useful for prevention of atherosclerotic cardiovascular diseases.