Cyclic phosphatidic acid inhibits the secretion of vascular endothelial growth factor from diabetic human coronary artery endothelial cells through peroxisome proliferator-activated receptor gamma

• Tsukahara, Tamotsu

• Tsukahara, Ryoko

• Haniu, Hisao

• Matsuda, Yoshikazu

• Murakami-Murofushi, Kimiko

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.

Molecular and Cellular Endocrinology, 412, pp.320-329; 2015

Journal

• Molecular and Cellular Endocrinology

  Molecular and Cellular Endocrinology 412 320-329, 2015-09-05

  Elsevier Ireland Ltd

Keywords

• Cyclic phosphatidic acid
• Diabetic human coronary artery endothelial cells
• Peroxisome proliferator-activated receptor gamma
• VEGF

Details

• CRID: 1050850247193740672
• NII Article ID: 120006986899
• ISSN: 03037207
• DOI: 10.1016/j.mce.2015.05.021
• HANDLE: 10069/35888
• Web Site: https://nagasaki-u.repo.nii.ac.jp/records/4748
• Web Site: https://api.elsevier.com/content/article/PII:S0303720715002889?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S0303720715002889?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN