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Role of autophagy in angiogenesis in aortic endothelial cells. Am J Physiol Cell Physiol 2012 Jan 15;302(2):C383-91

Date

10/28/2011

Pubmed ID

22031599

Pubmed Central ID

PMC3328843

DOI

10.1152/ajpcell.00164.2011

Abstract

Angiogenesis plays critical roles in the recovery phase of ischemic heart disease and peripheral vascular disease. An increase in autophagy is protective under hypoxic and chronic ischemic conditions. In the present study we determined the role of autophagy in angiogenesis. 3-Methyladenine (3-MA) and small interfering RNA (siRNA) against ATG5 were used to inhibit autophagy induced by nutrient deprivation of cultured bovine aortic endothelial cells (BAECs). Assays of BAECs tube formation and cell migration revealed that inhibition of autophagy by 3-MA or siRNA against ATG5 reduced angiogenesis. In contrast, induction of autophagy by overexpression of ATG5 increased BAECs tube formation and migration. Additionally, inhibiting autophagy impaired vascular endothelial growth factor (VEGF)-induced angiogenesis. However, inhibition of autophagy did not alter the expression of pro-angiogenesis factors such as VEGF, platelet-derived growth factor, or integrin αV. Furthermore, autophagy increased reactive oxygen species (ROS) formation and activated AKT phosphorylation. Inhibition of autophagy significantly decreased the production of ROS and activation of AKT but not of extracellular regulated kinase, whereas overexpression of ATG5 increased cellular ROS production and AKT activation in BAECs. Inhibition of AKT activation or ROS production significantly decreased the tube formation induced by ATG5 overexpression. Here we report a novel observation that autophagy plays an important role in angiogenesis in BAECs. Induction of autophagy promotes angiogenesis while inhibition of autophagy suppresses angiogenesis, including VEGF-induced angiogenesis. ROS production and AKT activation might be important mechanisms for mediating angiogenesis induced by autophagy. Our findings indicate that targeting autophagy may provide an important new tool for treating cardiovascular disease.

Author List

Du J, Teng RJ, Guan T, Eis A, Kaul S, Konduri GG, Shi Y

Authors

Girija Ganesh Konduri MD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Ru-Jeng Teng MD Associate Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenine
Animals
Aorta
Autophagy
Cattle
Cells, Cultured
Endothelial Cells
Extracellular Signal-Regulated MAP Kinases
Integrin alphaV
Microtubule-Associated Proteins
Neovascularization, Physiologic
Platelet-Derived Growth Factor
Proto-Oncogene Proteins c-akt
RNA, Small Interfering
Reactive Oxygen Species
Vascular Endothelial Growth Factor A
jenkins-FCD Prod-480 9a4deaf152b0b06dd18151814fff2e18f6c05280