Transcriptional Regulators of Angiogenesis

Hamik, Anne; Wang, Baiqiu; Jain, Mukesh K.

doi:10.1161/01.atv.0000232542.42968.e3

Cited by 66 publications

(48 citation statements)

References 107 publications

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“…ID family genes regulate cell cycle and cell fate, and they play essential roles in angiogenesis (3,24,39). Specifically, it has been demonstrated that ID1 can increase the proliferation activity of endothelial cells (45,52) and also preserve endothelial cell commitment in stem cell derived endothelial cells (31).…”

Section: Discussionmentioning

confidence: 99%

Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude

Zhang

Friedman

2012

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang J, Friedman MH. Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude. Am J Physiol Heart Circ Physiol 302: H983-H991, 2012. First published December 2, 2011; doi:10.1152/ajpheart.00168.2011.-The adaptation of vascular endothelial cells to shear stress alteration induced by global hemodynamic changes, such as those accompanying exercise or digestion, is an essential component of normal endothelial physiology in vivo. An understanding of the transient regulation of endothelial phenotype during adaptation to changes in mural shear will advance our understanding of endothelial biology and may yield new insights into the mechanism of atherogenesis. In this study, we characterized the adaptive response of arterial endothelial cells to an acute increase in shear stress magnitude in well-defined in vitro settings. Porcine endothelial cells were preconditioned by a basal level shear stress of 15 Ϯ 15 dyn/cm 2 at 1 Hz for 24 h, after which an acute increase in shear stress to 30 Ϯ 15 dyn/cm 2 was applied. Endothelial permeability nearly doubled after 40-min exposure to the elevated shear stress and then decreased gradually. Transcriptomics studies using microarray techniques identified 86 genes that were sensitive to the elevated shear. The acute increase in shear stress promoted the expression of a group of anti-inflammatory and antioxidative genes. The adaptive response of the global gene expression profile is triphasic, consisting of an induction period, an early adaptive response (ca. 45 min) and a late remodeling response. Our results suggest that endothelial cells exhibit a specific phenotype during the adaptive response to changes in shear stress; this phenotype is different than that of fully adapted endothelial cells. permeability; gene expression; microarray ATHEROSCLEROSIS ARISES FROM endothelial cell dysfunction. Endothelial dysfunction features increased permeability, enhanced expression of adhesion molecules and leukocyte adhesion, enhanced cell turnover, increased oxidant stress, and reduced endothelium-dependent vasodilation (51). Increased endothelial permeability leads to the accumulation of LDL in the intima, which is a key step in atherosclerotic development. The inflammatory response of endothelial cells results in the recruitment of monocytes, which migrate into the intima and differentiate into macrophages, which engulf oxidized LDL and form foam cells. The accumulation of foam cells in the intima leads to the formation of atherosclerotic plaques. Therefore, endothelial permeability and inflammatory status greatly affect arterial atherosusceptibility.Endothelial cells in the vasculature are constantly exposed to shear stress. Shear-dependent permeability to macromolecules has been examined both in vitro and in vivo. The application of shear stress to static cultured cells increased endothelial permeability to albumin (32) and dextran (50). However, these increases may have been caused by the transient response of endothelial cells to the onset of shear...

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Section: Discussionmentioning

confidence: 99%

Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude

Zhang

Friedman

2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…Results indicate that KROX (a component of the early growth response genes [EGR] family) regulates a significant amount of the genes whose methylation status correlates with blood flow, capillary density, and arteriole counts (418, 1979, and 369, respectively). 14,15 Moreover, 536 genes associated with blood flow, 2805 genes associated with capillary density, and 460 genes associated with arteriole counts are regulated by MYCassociated zinc finger protein (MAZ), which is involved in cell proliferation and mediates vascular endothelial growth factor (VEGF)-induced angiogenesis. 16 Hence, interference of DNA methylation with KROX/EGR1 and MAZ might result in large effects on gene transcription and possibly on promotion of tissue repair by SV-APCs.…”

Section: Correlation Between Dna Methylation Profile Of Sv-apcs and Pmentioning

confidence: 99%

Epigenetic Profile of Human Adventitial Progenitor Cells Correlates With Therapeutic Outcomes in a Mouse Model of Limb Ischemia

Gubernator

Slater

Spencer

et al. 2015

ATVB

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Objective— We investigated the association between the functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) and therapeutic activity in a model of limb ischemia. Approach and Results— Antigenic and functional features were analyzed throughout passaging in 15 saphenous vein (SV)–derived APC lines, of which 10 from SV leftovers of coronary artery bypass graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were transplanted (8×10 5 cells, IM) in mice with limb ischemia. Blood flow and capillary and arteriole density were correlated with functional characteristics and DNA methylation/expressional markers of transplanted cells. We report successful expansion of tested lines, which reached the therapeutic target of 30 to 50 million cells in ≈10 weeks. Typical antigenic profile, viability, and migratory and proangiogenic activities were conserved through passaging, with low levels of replicative senescence. In vivo, SV-APC transplantation improved blood flow recovery and revascularization of ischemic limbs. Whole genome screening showed an association between DNA methylation at the promoter or gene body level and microvascular density and to a lesser extent with blood flow recovery. Expressional studies highlighted the implication of an angiogenic network centered on the vascular endothelial growth factor receptor as a predictor of microvascular outcomes. FLT-1 gene silencing in SV-APCs remarkably reduced their ability to form tubes in vitro and support tube formation by human umbilical vein endothelial cells, thus confirming the importance of this signaling in SV-APC angiogenic function. Conclusions— DNA methylation landscape illustrates different therapeutic activities of human APCs. Epigenetic screening may help identify determinants of therapeutic vasculogenesis in ischemic disease.

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“…[5][6][7] Histone deacetylases (HDACs) act as critical transcriptional cofactors that are recruited to promoters by sequence-specific transcription factors to regulate gene expression. By removing acetyl groups from nucleosomal histones, HDACs counteract the stimulatory effects of histone acetyltransferases (HATs) resulting in chromatin condensation with consequent transcriptional repression.…”

Section: Histone Deacetylases and Vascular Endothelial Homeostasismentioning

confidence: 99%

Emerging roles of SIRT1 in vascular endothelial homeostasis

Potente

Dimmeler²

2008

Cell Cycle

145

106

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Transcriptional Regulators of Angiogenesis

Cited by 66 publications

References 107 publications

Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude

Adaptive response of vascular endothelial cells to an acute increase in shear stress magnitude

Epigenetic Profile of Human Adventitial Progenitor Cells Correlates With Therapeutic Outcomes in a Mouse Model of Limb Ischemia

Emerging roles of SIRT1 in vascular endothelial homeostasis

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