The prevalence of obesity is rising dramatically in developed and developing countries. Obesity contributes to increased mortality from numerous causes, but the most important of these is cardiovascular death. The relationship between obesity and atherogenesis is multifactorial, including alterations in the composition and level of lipoproteins, changes in blood pressure, and changes in circulating coagulation and inflammatory factors. Mouse models can be useful for dissecting selected aspects of this complex relationship. One area in which these models can be of particular value is in investigating the effect of secretory products of adipose tissue on the vessel wall. Adipocytes and adipose tissue secrete numerous factors and their level of expression is altered in obese states. Adipose tissue and adipocytes produce adiponectin, resistin, leptin, and apolipoproteins (serum amyloid A and apoE); all of which can directly impact vessel wall homeostasis. Mouse models utilizing deletion or overexpression of many of these factors have demonstrated an important impact of these on vessel wall homeostasis. Subsequent to the development of obesity, factors secreted from adipose tissue have also been shown to have direct effect on liver production of systemic inflammatory factors. Mouse models have validated the importance of angiotensin II, TNFα, and MCP-1 for impacting vessel wall health in obese states. In summary, excess adipose tissue produces myriad changes in organismal homeostasis with potential impact on the vessel wall. The power of mouse genetics permits targeted mechanistic investigation for understanding how obesity accelerates atherosclerosis in a complex in vivo milieu.
Keywords: obesity, atherosclerosis, adipokines, leptin, adiponectin, resistin, apolipoproteins
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