Vascular endothelium as a target of beraprost sodium and fenofibrate for antiatherosclerotic therapy in type 2 diabetes mellitus.
Diabetes mellitus is an important risk factor for cardiovascular morbidity and mortality. The metabolic abnormalities caused by diabetes mellitus induce vascular endothelial dysfunction that predisposes patients with diabetes mellitus to atherosclerosis. Two mega clinical trials showed that intensive glycemic control does not have favorable effects on reducing macrovascular events although it demonstrated significant reductions in microvascular complications. It is becoming worthwhile to clarify the beneficial effects of tight controls on blood pressure, serum lipids, and postprandial hyperglycemia to prevent atherosclerosis in patients with type 2 diabetes mellitus. Here, we focus on vascular endothelium as a target of the prostaglandin I2 analog beraprost sodium and the peroxisome proliferators-activated receptor alpha activator fenofibrate for the prevention and treatment of atherosclerosis in patients with type 2 diabetes mellitus. Beraprost sodium lowered circulating vascular cell adhesion molecule- 1 (VCAM-1) concentration and prevented the progression of carotid atherosclerosis in type 2 diabetic patients, probably through inhibiting VCAM-1 expression in vascular endothelium. Fenofibrate up-regulated endothelial nitric oxide synthase expression, which may explain its effects to improve endothelium-dependent vasodilatation and to prevent the progression of coronary atherosclerosis. The approaches to target the molecules expressed in vascular endothelium will become important for preventing the atherosclerosis in type 2 diabetes mellitus.
Otsuki
Michio
M
Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.
Goya
Kayoko
K
Kasayama
Soji
S
D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000209:etiology / Q000517:prevention & control*; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D011345:Fenofibrate / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; C048081:beraprost; D011464:Epoprostenol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D011345:Fenofibrate