Targeting MCP-1 to reduce vascular complications of obesity.
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.
Ohman
Miina K
MK
Department of Internal Medicine, Division of Cardiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Eitzman
Daniel T
DT
D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000378:metabolism; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D014652:Vascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*
D019440:Anti-Obesity Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2