Dataset Information

Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs.

ABSTRACT: Although the critical role of hypoxia inducible factor-1α (HIF-1α) in cerebral neovascularization after stroke has been well characterized, the details regarding the regulation of endothelial progenitor cell (EPC)-dependent neovascularization by HIF-1α are not completely understood. Using lentiviral shRNA to knockdown HIF-1α, we showed that HIF-1α plays a central role in bone marrow-derived EPC (bmEPC) homing and sprouting in the post-acute stage of ischemic Sprague Dawley (SD) rat brains. First, knockdown of HIF-1α decreased the homing of both endogenous and exogenous bmEPCs to the ischemic brain. Additionally, the knockdown impaired the incorporation and sprouting of bmEPCs in the ischemic brain. In vitro, knockdown of HIF-1α inhibited the spheroid sprouting and tube formation of bmEPCs. Mechanically, the HIF-1α-dependent recruitment of bmEPCs to the ischemic brain was relative to the CXCL12/CXCR4 axis and HMGB1, which were relative to astrocytes. In addition, the loss of HIF-1α resulted in deficient expression levels of VEGF-A, Flk-1, NRP1, and Dll4 in the ischemic brains, bmEPCs, and astrocytes. These findings suggested that HIF-1α implicates in bmEPC homing via CXCL12/CXCR4 and HMGB1 and that it promotes bmEPC sprouting via VEGF-A/flk1-NRP1/Dll4.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8028501 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs.

Liu Yang Y Ran He H Xiao Yaping Y Wang Hongjin H Chen Yi Y Chen Weihai W Xu Xiaoyu X

Brain pathology (Zurich, Switzerland) 20181009 6

Although the critical role of hypoxia inducible factor-1α (HIF-1α) in cerebral neovascularization after stroke has been well characterized, the details regarding the regulation of endothelial progenitor cell (EPC)-dependent neovascularization by HIF-1α are not completely understood. Using lentiviral shRNA to knockdown HIF-1α, we showed that HIF-1α plays a central role in bone marrow-derived EPC (bmEPC) homing and sprouting in the post-acute stage of ischemic Sprague Dawley (SD) rat brains. First ...[more]

PMID: 30052311

Similar Datasets

Project description:Increased dietary salt intake is a well-established risk factor for hypertension and related cardiovascular diseases, involving complex vascular remodeling processes. However, the specific role of hypoxia-inducible factor-1α (HIF-1α) in vascular pathophysiology under high-salt conditions remains poorly understood. This study investigates the role of HIF-1α in high-salt-induced vascular remodeling using human aortic vascular smooth muscle cells (HA-VSMCs) cultured in vitro. HA-VSMCs were divided into three groups: high-salt with HIF-1α knockdown (shHIF-1α + HS), negative control (shcontrol), and high-salt (HS). Cell viability, migration, gene expression, and protein levels were evaluated. High-salt conditions significantly increased mRNA expression of α-smooth muscle actin (α-SMA), smooth muscle protein 22 (SM22), angiotensin II type 1 receptor (AT1R), collagen I, and collagen III (p < 0.0001). HIF-1α knockdown partially attenuated these increases, particularly for α-SMA, SM22, and AT1R (p < 0.01). At the protein level, high-salt exposure markedly elevated expression of collagen III, HIF-1α, osteopontin (OPN), and angiotensin II (Ang II) (p < 0.0001). HIF-1α knockdown significantly reduced the high-salt-induced increases in collagen III and HIF-1α protein levels (p < 0.001) but had a limited effect on OPN and Ang II upregulation. Interestingly, SM22 protein expression was significantly decreased under high-salt conditions (p < 0.0001), an effect partially reversed by HIF-1α knockdown (p < 0.0001). These findings demonstrate that high-salt conditions induce complex changes in gene and protein expression in HA-VSMCs, with HIF-1α playing a crucial role in mediating many of these alterations. The study highlights the differential effects of HIF-1α on various markers of vascular remodeling and suggests that HIF-1α may be a potential therapeutic target for mitigating salt-induced vascular pathology. Further research is warranted to elucidate the mechanisms underlying the HIF-1α-dependent and -independent effects observed in this study.

Dataset Information

Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs.

Publications

Knockdown of HIF-1α impairs post-ischemic vascular reconstruction in the brain via deficient homing and sprouting bmEPCs.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets