PTEN silencing reverses aging-related impairment of angiogenesis in microvascular endothelial cells.
Aging is associated with impaired angiogenesis (new blood vessels formation from the endothelial cells of pre-existing vessels) in a variety of tissues. The precise mechanisms of aging-related impairment of angiogenesis are not known. PTEN is a dual-specificity phosphatase that antagonizes in some cells the PI3K/Akt signaling pathway, important for cell survival, function and angiogenesis. PTEN's role in aging-related impairment of angiogenesis is not known. In this study, we investigated whether expression of PTEN in endothelial cells may play a mechanistic role in aging-related impairment of angiogenesis. We demonstrated that human microvascular endothelial cells (HMVEC) derived from aging individuals (Aged-HMVEC) have: (1) significantly increased PTEN mRNA and protein levels and (2) impaired in vitro angiogenesis vs. neonatal derived HMVEC (Neo-HMVEC), and that (3) downregulation of PTEN using specific siRNA restores angiogenesis in Aged-HMVEC to normal. This is the first demonstration of increased PTEN expression in human microvascular endothelial cells derived from aging tissues and that elevated PTEN is a major factor responsible for aging-related impairment of in vitro angiogenesis.
Tarnawski
Andrzej S
AS
Medical Service, VALBHS and Department of Medicine, University of California Irvine, Long Beach, CA 90822, USA. atarnawski@yahoo.com
Pai
Rama
R
Tanigawa
Tetsuya
T
Matysiak-Budnik
Tamara
T
Ahluwalia
Amrita
A
D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics* / Q000473:pathology; D002196:Capillaries / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing; D006801:Humans; D008297:Male; D018919:Neovascularization, Physiologic / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human