The macrophage at the crossroads of insulin resistance and atherosclerosis.
The macrophage has emerged as an important player in the pathogenesis of both atherosclerosis and insulin resistance. Cross-talk between inflammatory macrophages and adipocytes may be involved in insulin resistance in peripheral tissues. Defective insulin signaling in cells of the arterial wall including macrophages may promote the development of atherosclerosis. Insulin resistant macrophages are more susceptible to endoplasmic reticulum stress and apoptosis in response to various stimuli such as nutrient deprivation, free cholesterol loading, and oxidized LDL. Increased apoptosis of insulin resistant macrophages and impaired phagocytic clearance of apoptotic cells by insulin resistant macrophages in atherosclerotic lesions may lead to enhanced postapoptotic necrosis, larger lipid-rich cores, increased inflammation, and more complex vulnerable plaques.
Liang
Chien-Ping
CP
Division of Molecular Medicine, Department of Medicine, Columbia University, New York, NY 10032, USA. CL534@columbia.edu
Han
Seongah
S
Senokuchi
Takafumi
T
Tall
Alan R
AR
D000818:Animals; D017209:Apoptosis; D050197:Atherosclerosis / Q000503:physiopathology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D018450:Disease Progression; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007333:Insulin Resistance; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D015398:Signal Transduction