Abstract 309: Sirt3 Regulates Oxygen Sensors and Blood Vessel Formation in the Heart

New blood vessels formation is driven by deprivation of nutrients and oxygen during myocardial ischemia. The interaction between nutrients and oxygen sensors in the regulation of new blood vessel formation still remains incompletely understood. Sirtuins belong to a family of NAD+-dependent deacetylases which are involved in the regulation of angiogenesis and energy hemostasis. In the present study, we investigated the functional role of Sirtuin 3 (Sirt3), a metabolic sensor, in the regulation of blood vessel formation and its interaction with oxygen sensors-prolyl hydroxylases (PHDs)/hypoxia-inducible factors (HIFs) system. The levels of PHD1-3, HIFs, and angiogenic growth factors as well as blood vessel formation were examined in the hearts of Sirt3 knockout (Sirt3 KO) mice and wild type (WT) mice. Our data showed that the expression of angiopoietin-1 and angiopoietin-2 was significantly reduced, whereas the expression of Tie-2 and VEGF was unchanged in the hearts of Sirt3 KO mice compared to WT mice. Intriguingly, loss of Sirt3 had different effects on the PHDs/HIFs system. The expression of PHD1, PHD2, and HIF1α was significantly up-regulated, but PHD3 and HIF2α expression was down-regulated in Sirt3 KO mice. Ex vivo angiogenesis assay revealed that vessel outgrowth was significantly reduced in Sirt3 KO mice compared to WT mice. Our immunohistochemistry study further confirmed that the arteriole formation was significantly reduced in the hearts of Sirt3 KO mice compared to that in WT mice. This was accompanied by a reduction of cardiac ejection fraction (EF %) and fraction shortening (FS %). Moreover, the phosphorylation level of Akt was dramatically decreased together with increased Wnt7b, caspase-3 expression and apoptosis in the hearts of Sirt3 KO mice. Therefore, our data implicates that Sirt3 is important in controlling of blood vessel growth and cell survival by affecting oxygen sensors and angiopoietins expression in the heart.

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Bone marrow mononuclear cells are recruited to the sites of VEGF-induced neovascularization but are not incorporated into the newly formed vessels

Blood ◽

10.1182/blood-2005-08-3215 ◽

2006 ◽

Vol 107 (9) ◽

pp. 3546-3554 ◽

Cited By ~ 102

Author(s):

Lorena Zentilin ◽

Sabrina Tafuro ◽

Serena Zacchigna ◽

Nikola Arsic ◽

Lucia Pattarini ◽

...

Keyword(s):

Bone Marrow ◽

Blood Vessel ◽

Mononuclear Cells ◽

Ex Vivo ◽

Experimental Models ◽

Large Set ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Sprouting Angiogenesis ◽

Vasculogenesis And Angiogenesis

Vascular endothelial growth factor (VEGF) is a key regulator of blood vessel formation during both vasculogenesis and angiogenesis. The prolonged expression of VEGF in the normoperfused skeletal muscles of adult rodents after gene transfer using AAV vectors induces the formation of a large set of new capillaries and small arteries. Notably, this process is accompanied by the massive infiltration by mononuclear cells. This observation raises the possibility that these cells might represent circulating progenitors that are eventually incorporated in the newly formed vessels. Here we explore this possibility by exploiting 4 different experimental models based on (a) the transplantation of male bone marrow into female recipients; (b) the transplantation of Tie2-GFP transgenic bone marrow; (c) the transplantation of bone marrow in the presence of erythropoietin (EPO), a mobilizer of endothelial progenitor cells (EPCs); and (d) the reimplantation of ex vivo–expanded EPCs. In all 4 models, VEGF acted as a powerful attractor of bone marrow–derived mononuclear cells, bearing different myeloid and endothelial markers proper of the EPCs to the sites of neovascularization. In no case, however, were the attracted cells incorporated in the newly formed vasculature. These observations indicate that new blood vessel formation induced by VEGF occurs through bona fide sprouting angiogenesis; the contribution of the infiltrating bone marrow–derived cells to this process still remains enigmatic.

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Arteriogenesis Versus Angiogenesis: Two Mechanisms of Vessel Growth

Physiology ◽

10.1152/physiologyonline.1999.14.3.121 ◽

1999 ◽

Vol 14 (3) ◽

pp. 121-125 ◽

Cited By ~ 6

Author(s):

I. Buschmann ◽

W. Schaper

Keyword(s):

Blood Vessel ◽

Peripheral Artery Disease ◽

Capillary Density ◽

Peripheral Artery ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Collateral Arteries ◽

Vessel Growth ◽

Artery Disease ◽

Growth Features

After birth, new blood vessel formation proceeds via angiogenesis or arteriogenesis. Angiogenesis (capillary sprouting) results in higher capillary density. Arteriogenesis (rapid proliferation of collateral arteries) is potentially able to significantly alter the outcome of coronary and peripheral artery disease. The processes share some growth features but differ in many aspects.

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Faculty Opinions recommendation of Cdc42 is required for cytoskeletal support of endothelial cell adhesion during blood vessel formation in mice.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725705389.793510324 ◽

2015 ◽

Author(s):

Guillermo Oliver ◽

Noelia Escobedo

Keyword(s):

Cell Adhesion ◽

Endothelial Cell ◽

Blood Vessel ◽

Blood Vessel Formation ◽

Vessel Formation ◽

Endothelial Cell Adhesion

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Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

International Journal of Molecular Sciences ◽

10.3390/ijms22062804 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2804

Author(s):

Yasuo Yoshitomi ◽

Takayuki Ikeda ◽

Hidehito Saito-Takatsuji ◽

Hideto Yonekura

Keyword(s):

Endothelial Cells ◽

Transcription Factor ◽

Blood Vessel ◽

Vascular Endothelial Cells ◽

Vascular Development ◽

Endothelial Cell Migration ◽

Vascular Endothelial ◽

Blood Vessel Formation ◽

Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

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Vascularization Strategies in Bone Tissue Engineering

Cells ◽

10.3390/cells10071749 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1749

Author(s):

Filip Simunovic ◽

Günter Finkenzeller

Keyword(s):

Tissue Engineering ◽

Blood Vessel ◽

Bone Tissue Engineering ◽

Bone Tissue ◽

Critical Size ◽

Ex Vivo ◽

Angiogenic Growth Factors ◽

Hypoxic Conditions ◽

Surgical Methods ◽

Artificial Tissue

Bone is a highly vascularized tissue, and its development, maturation, remodeling, and regeneration are dependent on a tight regulation of blood vessel supply. This condition also has to be taken into consideration in the context of the development of artificial tissue substitutes. In classic tissue engineering, bone-forming cells such as primary osteoblasts or mesenchymal stem cells are introduced into suitable scaffolds and implanted in order to treat critical-size bone defects. However, such tissue substitutes are initially avascular. Because of the occurrence of hypoxic conditions, especially in larger tissue substitutes, this leads to the death of the implanted cells. Therefore, it is necessary to devise vascularization strategies aiming at fast and efficient vascularization of implanted artificial tissues. In this review article, we present and discuss the current vascularization strategies in bone tissue engineering. These are based on the use of angiogenic growth factors, the co-implantation of blood vessel forming cells, the ex vivo microfabrication of blood vessels by means of bioprinting, and surgical methods for creating surgically transferable composite tissues.

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