title: Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma.
abstract: Atherosclerosis is a disease characterized by building up plaques formation and leads to a potentially serious condition in which arteries are clogged by fatty substances such as cholesterol. Increasing evidence suggests that atherosclerosis is accelerated in type 2 diabetes. Recent study reported that high level of alkyl glycerophosphate (AGP) was accumulated in atherosclerotic lesions. The presence of this phospholipid in mildly oxidized low-density lipoprotein (LDL) is likely to be involved in atherogenesis. It has been reported that the activation of peroxisome proliferator-activated receptor gamma plays a key role in developing atherosclerosis. Our previous result indicates that cyclic phosphatidic acid (cPA), one of bioactive lipids, potently suppresses neointima formation by inhibiting the activation of peroxisome proliferator-activated receptor gamma (PPARγ). However, the detailed mechanism is still unclear. In this study, to elucidate the mechanism of the cPA-PPARγ axis in the coronary artery endothelium, especially in patients with type 2 diabetes, we investigated the proliferation, migration, and secretion of VEGF in human coronary artery endothelial cells from diabetes patients (D-HCAECs). AGP induced cell growth and migration; however, cPA suppressed the AGP-elicited growth and migration in D-HCAECs. Moreover, AGP increased VEGF secretion from D-HCAECs, and this event was attenuated by cPA. Taken together, these results suggest that cPA suppresses VEGF-stimulated growth and migration in D-HCAECs. These findings could be important for regulatory roles of PPARγ and VEGF in the vascular processes associated with diabetes and atherosclerosis.
authors.affiliation: Department of Molecular Pharmacology and Neuroscience, Graduate School of Biomedical Sciences, Nagasaki University, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. Electronic address: ttamotsu@nagasaki-u.ac.jp.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Tsukahara
authors.affiliation: Endowed Research Division of Human Welfare Sciences, Ochanomizu University, 2-1-1, Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan; Science and Education Center, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-861, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Tsukahara
authors.affiliation: Institue for Biomedical Sciences, Shinshu University Interdisciplinary Cluster for Cutting Edge Research 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
authors.forename: Hisao
authors.initials: H
authors.lastname: Haniu
authors.affiliation: Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Matsuda
authors.affiliation: Science and Education Center, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-861, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000494:pharmacology; D006801:Humans; D047495:PPAR gamma / Q000502:physiology*; D010712:Phosphatidic Acids / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D006573:Heterocyclic Compounds, 1-Ring; D047495:PPAR gamma; D010712:Phosphatidic Acids; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Cyclic phosphatidic acid; Diabetic human coronary artery endothelial cells; Peroxisome proliferator-activated receptor gamma; VEGF