Endothelial cell response to lactate: Implication of PAR modification of VEGF

• Published in: Journal of cellular physiology 2007-05, Vol.211 (2), p.477-485
• Main Authors: Kumar, V.B. Sameer, Viji, R.I., Kiran, M.S., Sudhakaran, P.R.
• Format: Article
• Language: English
• Subjects: Angiogenesis Inducing Agents - metabolism; Angiogenesis Inducing Agents - pharmacology; Animals; Aorta, Thoracic - drug effects; Cells, Cultured; Chick Embryo; Chorioallantoic Membrane - blood supply; Chorioallantoic Membrane - metabolism; Dose-Response Relationship, Drug; Embryo Culture Techniques; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Enzyme-Linked Immunosorbent Assay; Humans; Lactic Acid - metabolism; Lactic Acid - pharmacology; NAD - metabolism; Neovascularization, Physiologic - drug effects; Phenotype; Poly Adenosine Diphosphate Ribose - metabolism; Poly(ADP-ribose) Polymerases - metabolism; Protein Processing, Post-Translational - drug effects; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Time Factors; Tissue Culture Techniques; Umbilical Veins - cytology; Umbilical Veins - metabolism; Up-Regulation; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics; Vascular Endothelial Growth Factor A - isolation & purification; Vascular Endothelial Growth Factor A - pharmacology; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vascular Endothelial Growth Factor Receptor-2 - genetics
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.20955

Angiogenesis, the process of formation of new blood vessels from pre‐existing one, occurs in many physiological and pathological conditions, most of which are underlined by hypoxia and resultant accumulation of lactate. Although lactate is known to induce angiogenesis, the mechanism of its action on endothelial cells (ECs) is not known. The present study was designed to examine the response of ECs to lactate. Morphological analysis revealed that human umbilical vein endothelial cells (HUVECs) in culture respond to lactate by switching over to angiogenic phenotype concomitant with upregulation of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor‐2 (VEGFR2) as determined by reverse transcription‐PCR (RT‐PCR). Apart from increase in the levels of VEGF protein as determined by ELISA, chorio allantoic membrane (CAM) assay using the cell extracts revealed that lactate also increased the angiogenic potency of VEGF. Isolated VEGF, when blotted and subsequently probed with anti‐PAR antibody, revealed considerable reduction in poly‐adenosyl ribosylation of VEGF associated with a significant decrease in the levels of NAD+, in presence of lactate. Thus it appears that ECs respond to lactate by increasing the production of VEGF and modulating its angiogenic potency through poly‐ADP ribosylation (PAR)‐dependent mechanism and thereby switch over to angiogenic phenotype. J. Cell. Physiol. 211: 477–485, 2007. © 2006 Wiley‐Liss, Inc.