Regulation of advanced glycation end product (AGE)-receptor (RAGE) system by PPAR-gamma agonists and its implication in cardiovascular disease.
Non-enzymatic modification of proteins by reducing sugars leads to the formation of advanced glycation end products (AGEs), whose process has been reported to progress under physiological aging, oxidative stress or diabetic conditions. There is a growing body of evidence that AGEs and their receptor (RAGE) axis is involved in the pathogenesis of cardiovascular disease (CVD). Indeed, engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory and thrombogenic responses in various types of cells, including endothelial cells, smooth muscle cells, macrophages and renal cells, thus playing an important role in the development and progression of vascular injury in both diabetes and non-diabetes. These observations suggest that the inhibition of AGE formation, down-regulation of RAGE expression or blockade of the RAGE downstream signaling may be a promising therapeutic target for preventing CVD. Recently, peroxisome proliferator-activated receptor-gamma (PPARgamma) is involved in not only adipocyte differentiation, but also vascular homeostasis. Therefore, in this study, we review effects of PPARgamma agonists on the AGE-RAGE system and their implication in CVD.
Yamagishi
Sho-ichi
S
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, 67 Asahi-machi, Kurume 830-0011, Japan. shoichi@med.kurume-u.ac.jp
Nakamura
Kazuo
K
Matsui
Takanori
T
D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002908:Chronic Disease; D048909:Diabetes Complications / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006331:Heart Diseases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects; D007674:Kidney Diseases / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000502:physiology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic