Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis

Abstract B-cell lymphoma 2 (Bcl-2) protein is the founding member of a group of proteins known to modulate apoptosis. Its discovery set the stage for identification of family members with either pro- or anti-apoptotic properties. Expression of Bcl-2 plays an important role during angiogenesis by inf...

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Autores principales:	Ismail S. Zaitoun, Catherine M. Wintheiser, Nasim Jamali, Shoujian Wang, Andrew Suscha, Soesiawati R. Darjatmoko, Katherine Schleck, Barbara A. Hanna, Volkhard Lindner, Nader Sheibani, Christine M. Sorenson
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/718ad2e315fb4f21a2f96f996666b937
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spelling	oai:doaj.org-article:718ad2e315fb4f21a2f96f996666b9372021-12-02T15:08:59ZBcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis10.1038/s41598-019-45915-42045-2322https://doaj.org/article/718ad2e315fb4f21a2f96f996666b9372019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45915-4https://doaj.org/toc/2045-2322Abstract B-cell lymphoma 2 (Bcl-2) protein is the founding member of a group of proteins known to modulate apoptosis. Its discovery set the stage for identification of family members with either pro- or anti-apoptotic properties. Expression of Bcl-2 plays an important role during angiogenesis by influencing not only vascular cell survival, but also migration and adhesion. Although apoptosis and migration are postulated to have roles during vascular remodeling and regression, the contribution of Bcl-2 continues to emerge. We previously noted that the impaired retinal vascularization and an inability to undergo pathologic neovascularization observed in mice globally lacking Bcl-2 did not occur when mice lacked the expression of Bcl-2 only in endothelial cells. To further examine the effect of Bcl-2 expression during vascularization of the retina, we assessed its contribution in pericytes or astrocytes by generating mice with a conditional Bcl-2 allele (Bcl-2Flox/Flox) and Pdgfrb-cre (Bcl-2PC mice) or Gfap-cre (Bcl-2AC mice). Bcl-2PC and Bcl-2AC mice demonstrated increased retinal vascular cell apoptosis, reduced numbers of pericytes and endothelial cells and fewer arteries and veins in the retina. Bcl-2PC mice also demonstrated delayed advancement of the superficial retinal vascular layer and aberrant vascularization of the deep vascular plexus and central retina. Although pathologic neovascularization in oxygen-induced ischemic retinopathy (OIR) was not affected by lack of expression of Bcl-2 in either pericytes or astrocytes, laser-induced choroidal neovascularization (CNV) was significantly reduced in Bcl-2PC mice compared to littermate controls. Together these studies begin to reveal how cell autonomous modulation of apoptosis in vascular cells impacts development and homeostasis.Ismail S. ZaitounCatherine M. WintheiserNasim JamaliShoujian WangAndrew SuschaSoesiawati R. DarjatmokoKatherine SchleckBarbara A. HannaVolkhard LindnerNader SheibaniChristine M. SorensonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ismail S. Zaitoun Catherine M. Wintheiser Nasim Jamali Shoujian Wang Andrew Suscha Soesiawati R. Darjatmoko Katherine Schleck Barbara A. Hanna Volkhard Lindner Nader Sheibani Christine M. Sorenson Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
description	Abstract B-cell lymphoma 2 (Bcl-2) protein is the founding member of a group of proteins known to modulate apoptosis. Its discovery set the stage for identification of family members with either pro- or anti-apoptotic properties. Expression of Bcl-2 plays an important role during angiogenesis by influencing not only vascular cell survival, but also migration and adhesion. Although apoptosis and migration are postulated to have roles during vascular remodeling and regression, the contribution of Bcl-2 continues to emerge. We previously noted that the impaired retinal vascularization and an inability to undergo pathologic neovascularization observed in mice globally lacking Bcl-2 did not occur when mice lacked the expression of Bcl-2 only in endothelial cells. To further examine the effect of Bcl-2 expression during vascularization of the retina, we assessed its contribution in pericytes or astrocytes by generating mice with a conditional Bcl-2 allele (Bcl-2Flox/Flox) and Pdgfrb-cre (Bcl-2PC mice) or Gfap-cre (Bcl-2AC mice). Bcl-2PC and Bcl-2AC mice demonstrated increased retinal vascular cell apoptosis, reduced numbers of pericytes and endothelial cells and fewer arteries and veins in the retina. Bcl-2PC mice also demonstrated delayed advancement of the superficial retinal vascular layer and aberrant vascularization of the deep vascular plexus and central retina. Although pathologic neovascularization in oxygen-induced ischemic retinopathy (OIR) was not affected by lack of expression of Bcl-2 in either pericytes or astrocytes, laser-induced choroidal neovascularization (CNV) was significantly reduced in Bcl-2PC mice compared to littermate controls. Together these studies begin to reveal how cell autonomous modulation of apoptosis in vascular cells impacts development and homeostasis.
format	article
author	Ismail S. Zaitoun Catherine M. Wintheiser Nasim Jamali Shoujian Wang Andrew Suscha Soesiawati R. Darjatmoko Katherine Schleck Barbara A. Hanna Volkhard Lindner Nader Sheibani Christine M. Sorenson
author_facet	Ismail S. Zaitoun Catherine M. Wintheiser Nasim Jamali Shoujian Wang Andrew Suscha Soesiawati R. Darjatmoko Katherine Schleck Barbara A. Hanna Volkhard Lindner Nader Sheibani Christine M. Sorenson
author_sort	Ismail S. Zaitoun
title	Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
title_short	Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
title_full	Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
title_fullStr	Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
title_full_unstemmed	Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
title_sort	bcl-2 expression in pericytes and astrocytes impacts vascular development and homeostasis
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/718ad2e315fb4f21a2f96f996666b937
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Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis

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