Induction of Angiogenesis by a Type III Phosphodiesterase Inhibitor, Cilostazol, Through Activation of Peroxisome Proliferator-Activated Receptor-γ and cAMP Pathways in Vascular Cells

Arteriosclerosis, Thrombosis, and Vascular Biology
Fumihiro SanadaRyuichi Morishita

Abstract

Peripheral arterial disease is highly prevalent in the elderly and in the subjects with cardiovascular risk factors such as diabetes. Approximately 2% to 4% of those affected with peripheral arterial disease commonly complain of intermittent claudication. Cilostazol, a type III phosphodiesterase inhibitor, is the only Food and Drug Administration-approved drug for the treatment of intermittent claudication. Cilostazol has been shown to be beneficial for the improvement of pain-free walking distance in patients with intermittent claudication in a series of randomized clinical trials. However, the underlying mechanism how cilostazol improved intermittent claudication symptoms is still unclear. In this study, the effect of cilostazol on ischemic leg was investigated in mouse ischemic hindlimb model. Administration of cilostazol significantly increased the expression of hepatocyte growth factor (HGF), vascular endothelial growth factor, angiopoietin-1, and peroxisome proliferator-activated receptor-γ in vasculature. The capillary density in ischemic leg was also significantly increased in cilostazol treatment group when compared with control and aspirin treatment group. However, an increase in capillary density and the expression o...Continue Reading

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Citations

Sep 29, 2017·Vascular Specialist International·George Galyfos, Argyri Sianou
Oct 26, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Hong S LuAlan Daugherty
Jul 1, 2020·Annals of Vascular Diseases·Fumihiro SanadaRyuichi Morishita
Jan 23, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Kenichiro ShimataniYoshiki Sawa
Oct 13, 2019·Current Medicinal Chemistry·Agnieszka JankowskaGrażyna Chłoń-Rzepa
Oct 22, 2021·Journal of Clinical Pharmacology·Antonis A ManolisAntonis S Manolis

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