High density lipoproteins in the intersection of diabetes mellitus, inflammation and cardiovascular disease.
OBJECTIVE
Low HDL-cholesterol, diabetes mellitus and elevated C-reactive protein as well as various inflammatory diseases are risk factors for coronary heart disease. Both diabetes mellitus and inflammation decrease HDL-cholesterol. We summarize recent findings on the mechanisms underlying low HDL-cholesterol in diabetes and inflammation, as well as on novel functions of HDL that may protect not only from atherosclerosis but also from diabetes mellitus and inflammation-induced organ damage.


RESULTS
Elevated levels of non-esterified fatty acids and disturbed insulin action contribute to low HDL-cholesterol in diabetes mellitus by modifying lipolysis, apolipoprotein A-I production, as well as the activities of adenosine triphosphate-binding cassette transporter A1 and lipid transfer. Inflammation causes low HDL-cholesterol by increasing the activities of endothelial lipase and soluble phospholipase A2 and by replacing apolipoprotein A-I in HDL with serum amyloid A. HDL and lysosphingolipids therein have been identified as activators of the protein kinase Akt, which in turn is a regulator of apoptosis in beta-cells, endothelial cells, and smooth muscle cells, as well as a regulator of nitric oxide production and adhesion molecule expression in endothelial cells.


CONCLUSIONS
The protective properties of HDL in cytokine production, lipid oxidation, cholesterol efflux and reverse cholesterol transport make HDL a protective agent in inflammation-induced organ damage including diabetes mellitus. However, inflammation and diabetes cause a decrease in HDL-cholesterol concentrations and impair HDL function, placing HDL into the centre of a vicious cycle that may escalate into diabetes mellitus, inflammation-induced organ damage and atherosclerosis.
Rohrer
Lucia
L
Institute of Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, CH-8091 Zurich, Switzerland.
Hersberger
Martin
M
von Eckardstein
Arnold
A
D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D003920:Diabetes Mellitus / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008075:Lipoproteins, HDL / Q000378:metabolism*
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002097:C-Reactive Protein