Role of triglyceride-rich lipoproteins in diabetic nephropathy.
Diabetic nephropathy is an increasingly important cause of morbidity and mortality worldwide. A large body of evidence suggests that dyslipidemia has an important role in the progression of kidney disease in patients with diabetes. Lipids may induce renal injury by stimulating TGF-beta, thereby inducing the production of reactive oxygen species and causing damage to the glomeruli and glomerular glycocalyx. Findings from basic and clinical studies strongly suggest that excess amounts of a variety of lipoproteins and lipids worsens diabetes-associated microvascular and macrovascular disease, increases glomerular injury, increases tubulointerstitial fibrosis, and accelerates the progression of diabetic nephropathy. The increasing prevalence of obesity, type 2 diabetes mellitus, and diabetic nephropathy means that interventions that can interrupt the pathophysiological cascade of events induced by lipoproteins and lipids could enable major life and cost savings. This Review discusses the structural, cellular, and microscopic findings associated with diabetic nephropathy and the influence of lipoproteins, specifically triglyceride-rich lipoproteins (TGRLs), on the development and perpetuation of diabetic nephropathy. Some of the accepted and hypothesized mechanisms of renal injury relating to TGRLs are also described.
Rutledge
John C
JC
Division of Cardiovascular Medicine, University of California Davis School of Medicine, University of California, Davis, CA 95616, USA. jcrutledge@ucdavis.edu
Ng
Kit F
KF
Aung
Hnin H
HH
Wilson
Dennis W
DW
D000818:Animals; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism*
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D014280:Triglycerides; C030087:lipoprotein triglyceride