HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes.

@article{Shimoda2006HIF1RH,
  title={HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes.},
  author={Larissa A. Shimoda and Michele Fallon and Sarah Pisarcik and Jian Wang and Gregg L. Semenza},
  journal={American journal of physiology. Lung cellular and molecular physiology},
  year={2006},
  volume={291 5},
  pages={
          L941-9
        }
}
Vascular remodeling resulting from altered pulmonary arterial smooth muscle cell (PASMC) growth is a contributing factor to the pathogenesis of hypoxic pulmonary hypertension. PASMC growth requires an alkaline shift in intracellular pH (pH(i)) and we previously showed that PASMCs isolated from mice exposed to chronic hypoxia exhibited increased Na(+)/H(+) exchanger (NHE) expression and activity, which resulted in increased pH(i). However, the mechanism by which hypoxia caused these changes was… 
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Results show that contrary to reports in other cell types, in PASMCs, AQP1 does not appear to be a direct target for HIF transcriptional regulation and may be upregulated by a mechanism involving HIF-dependent increases in [Ca2+]i.
Hypoxia-inducible factor-1α in pulmonary arterial smooth muscle cells and hypoxia-induced pulmonary hypertension.
TLDR
The role of HIF-1α in the pulmonary arterial smooth muscle cells (PASMC) is demonstrated to be specifically required in PASMC for the development of HPH, and the attenuation of pulmonary hypertension may be due to decreased pulmonary vasoconstriction in response to hypoxia in the Hif-1 α-SMM-Cre mice.
Deficiency of the NHE1 gene prevents hypoxia-induced pulmonary hypertension and vascular remodeling.
TLDR
It is demonstrated that deficiency of the NHE1 gene prevented the development of hypoxia-induced pulmonary hypertension and vascular remodeling in mice and revealed a novel regulatory pathway associated with N HE1 signaling.
Role of Rho kinase and Na+/H+ exchange in hypoxia‐induced pulmonary arterial smooth muscle cell proliferation and migration
TLDR
The role of the Na+/H+ exchanger (NHE) and alterations in intracellular pH (pHi) homeostasis in meditating increased proliferation and migration in PASMCs isolated from resistance‐sized pulmonary arteries from chronically hypoxic rats or from normoxic rats that were exposed to hypoxia ex vivo.
Molecular mechanisms of hypoxia‐inducible factor‐induced pulmonary arterial smooth muscle cell alterations in pulmonary hypertension
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This review addresses the relationship of hypoxia and the HIF system with pulmonary arterial dysfunction in PH and focuses on the cellular and molecular mechanisms underlying the Hif‐driven pathophysiological processes.
Activation of hypoxia-inducible factor-1 in pulmonary arterial smooth muscle cells by endothelin-1.
TLDR
The results suggest that ET-1 induces a PASMC-specific increase in HIF-1α levels by upregulation of Hif-1 α synthesis and downregulation of PHD2-mediated degradation, thereby amplifying the induction of HIFs during moderate, prolonged hypoxia.
Regulation of hypoxia-induced pulmonary hypertension by vascular smooth muscle hypoxia-inducible factor-1α.
TLDR
Results indicate that Hif-1α in smooth muscle contributes to pulmonary vascular remodeling and pulmonary hypertension in chronic hypoxia, however, loss of HIF-1 function in smooth Muscle does not affect hypoxic cardiac remodeling, suggesting that the cardiac hypertrophy response is not directly coupled to the increase in pulmonary artery pressure.
The Na+/H+ exchanger contributes to increased smooth muscle proliferation and migration in a rat model of pulmonary arterial hypertension
TLDR
It is suggested that increased NHE activity contributes to pathologic PASMC function in the SuHx model of PAH, although this effect does not appear to be mediated by global changes in pHi homeostasis.
Digoxin inhibits development of hypoxic pulmonary hypertension in mice
TLDR
Preclinical data support a role for HIF-1 inhibitors in the treatment of HPH and attenuated the hypoxia-induced increases in RV pressure and PASMC pH and [Ca2+]i.
Iptakalim induces mitochondria-dependent apoptosis in hypoxic rat pulmonary arterial smooth muscle cells.
  • Qi Xu, Xiang Wu, +4 authors Hong Wang
  • Biology
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2016
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