Ohman Miina K, Eitzman Daniel T
Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Recent Pat Cardiovasc Drug Discov. 2009 Nov;4(3):164-76. doi: 10.2174/157489009789152230.
Obesity is a risk factor for complications of atherosclerotic vascular disease such as myocardial infarction. Recent studies and several patents have demonstrated that the cardiovascular risk associated with obesity is correlated particularly with visceral adiposity. Excess visceral adiposity may increase vascular risk due to secretion of cytokines and chemokines by cellular constituents of the adipose tissue. The secretory profile of various adipose depots may be regulated by the influx of macrophages that has been shown to occur with expansion of fat stores. This macrophage infiltration may lead to a chronic low grade, systemic, inflammatory state. Since circulating markers of inflammation are associated with cardiovascular events, the inflammation triggered by visceral fat may contribute to an increased risk for vascular complications. While the vasculopathic effects of central obesity may be best treated by weight loss, long term weight loss is difficult to achieve, even with currently available pharmacotherapies. Therapies that target macrophage accumulation in fat or secretory products of adipose tissue may be potentially beneficial in reducing the vascular risk associated with obesity. A potential therapeutic target is monocyte chemoattractant 1 (MCP-1), which is a potent chemokine that is elevated in obesity. Since MCP-1 promotes atherosclerosis, inhibition of MCP-1 may be effective in reducing the vascular risk associated with obesity.
肥胖是动脉粥样硬化性血管疾病并发症（如心肌梗死）的一个风险因素。最近的研究和多项专利表明，与肥胖相关的心血管风险尤其与内脏脂肪过多有关。内脏脂肪过多可能会因脂肪组织细胞成分分泌细胞因子和趋化因子而增加血管风险。各种脂肪储存部位的分泌特征可能受巨噬细胞流入的调节，研究表明巨噬细胞流入会随着脂肪储存的增加而发生。这种巨噬细胞浸润可能导致慢性低度全身性炎症状态。由于循环炎症标志物与心血管事件相关，内脏脂肪引发的炎症可能会增加血管并发症的风险。虽然中心性肥胖的血管病变影响可能通过减肥得到最佳治疗，但即使采用目前可用的药物疗法，长期减肥也很难实现。针对脂肪中巨噬细胞积聚或脂肪组织分泌产物的疗法可能对降低与肥胖相关的血管风险具有潜在益处。一个潜在的治疗靶点是单核细胞趋化蛋白1（MCP-1），它是一种在肥胖状态下升高的强效趋化因子。由于MCP-1促进动脉粥样硬化，抑制MCP-1可能有效降低与肥胖相关的血管风险。
