Regulation of high-density lipoprotein by inflammatory cytokines: establishing links between immune dysfunction and cardiovascular disease.
Coronary artery disease is a primary co-morbidity in metabolic diseases such as metabolic syndrome, diabetes and obesity. One contributing risk factor for coronary artery disease is low high-density lipoprotein-cholesterol (HDLc). Several factors influence steady-state HDLc levels, including diet, genetics and environment. Perhaps more important to coronary artery disease is factors that attribute to the dynamics of reverse cholesterol transport, storage, and excretion of excess cholesterol. HDLc biogenesis, clearance and innate ability to serve as a cholesterol acceptor and transporter all contribute to HDLc's function as a negative regulator of cardiovascular disease. With the recent failure of torcetrapid, focus is being placed on HDLc biology and its role in various metabolic diseases. Low HDLc levels are often associated with an increased state of background inflammation. Recently, several syndromes with clear pro-inflammatory components have been shown to be inversely correlated with low HDLc levels in the absence of obesity, diabetes and metabolic syndrome. Early studies with HDLc during the acute-phase response suggest that HDLc is substantially physically modified during acute infection and sepsis, and recent studies show that HDLc is physically modified by chronic pro-inflammatory disease. In this review, several of these connections are described and cytokine signalling related to HDLc is examined.
Haas
Michael J
MJ
Department of Medicine, University of Florida College of Medicine, 653-1 West Eighth Street, Jacksonville, FL 32209, USA. michael.haas@jax.ufl.edu
Mooradian
Arshag D
AD
D000210:Acute-Phase Reaction; D016632:Apolipoprotein A-I / Q000235:genetics; D050197:Atherosclerosis / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D008076:Cholesterol, HDL / Q000378:metabolism* / Q000502:physiology; D003324:Coronary Artery Disease / Q000503:physiopathology; D016207:Cytokines / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008075:Lipoproteins, HDL; D009765:Obesity / Q000150:complications / Q000503:physiopathology; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000627:therapeutic use
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D016207:Cytokines; D008075:Lipoproteins, HDL; D045162:Thiazolidinediones