Advanced glycosylation endproducts in diabetic renal disease: clinical measurement, pathophysiological significance, and prospects for pharmacological inhibition.
Glucose reacts nonenzymatically with amino groups to produce a class of stable, crosslinking moieties termed advanced glycosylation endproducts (AGEs). These products act to increase vascular permeability, enhance subintimal protein and lipoprotein deposition, inactivate nitric oxide, and exert a number of toxic effects of endothelial cells. Loss of normal renal function has been found recently to cause a marked increase in the circulating levels of plasma AGEs, suggesting that these moieties may comprise one component of the so-called uremic 'middle molecules'. AGEs also form on the lipid and the protein components of LDL, forming a modified form of LDL (AGE-LDL) which is not taken up by tissue LDL receptors. Aminoguanidine offers a specific therapeutic modality for inhibiting advanced glycosylation in vivo and has been observed recently to reduce both hemoglobin-AGE and circulating LDL levels.
Bucala
R
R
Picower Institute of Medical Research, Manhasset, N.Y. 11030, USA.
Vlassara
H
H
D000818:Animals; D002241:Carbohydrates / Q000009:adverse effects / Q000096:biosynthesis* / Q000097:blood; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects; D006031:Glycosylation; D006146:Guanidines / Q000627:therapeutic use; D006801:Humans; D008074:Lipoproteins / Q000187:drug effects / Q000378:metabolism
D002241:Carbohydrates; D006146:Guanidines; D008074:Lipoproteins; C004479:pimagedine