Mitochondrial metabolism, redox signaling, and fusion: a mitochondria-ROS-HIF-1alpha-Kv1.5 O2-sensing pathway at the intersection of pulmonary hypertension and cancer.
These studies implicate HIF-1 in pathophysiologic alterations of both smooth muscle and endothelial cell biology in patients with pulmonary hypertension.
BMP4 acts downstream of HIF-1 and mediates hypoxia-induced up-regulation of TRPC, leading to increased basal [Ca(2+)]i in PASMCs, promoting CHPH pathogenesis.
Hypoxia inducible factor-1α (HIF-1α) pathway is associated with many vascular diseases, including atherosclerosis, arterial aneurysms, pulmonary hypertension and chronic venous diseases.
It is concluded that miR-429 is an important upstream mediator in PHD2/HIF-1α-associated renal adaptation to high salt intake and that deficiency in miR-429-mediated PHD2 inhibition in response to high salt in the renal medulla may represent a pathogenic mechanism for salt-sensitive hypertension.
Impaired pressure natriuresis (PN) underlies salt-sensitive hypertension, and renal inflammation and hypoxia-inducible factor-1 (HIF-1) have been implicated in the modulation of systemic hypertension.
Endothelial <i>Hif2a</i> knockout prevented hypoxia-induced pulmonary hypertension in mice.Inhibition of HIF2 (but not HIF1) can provide a therapeutic approach to prevent the development of hypoxia-induced pulmonary hypertension.
Accumulation of hypoxia inducible factor-1α (HIF-1α) is commonly an acute and beneficial response to hypoxia, whereas chronically elevated HIF-1α is associated with multiple disease conditions, including preeclampsia, a serious hypertensive disease of pregnancy.
Recently, proangiogenic factors hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) have been known to promote left ventricular myocardial angiogenesis and lead to cardiac hypertrophy, and this would be involved in RV hypertrophy of PH patients.
These observations suggest that altered glucose metabolism and G6PD overactivation play a key role in switching the PASM cells from the contractile to synthetic phenotype by increasing Sp1 and HIF-1α, which suppresses myocardin, a key cofactor that maintains smooth muscle cell in contractile state, and increasing hypoxia-induced PASM cell growth, and hence contribute to pulmonary arterial remodeling and pathogenesis of pulmonary hypertension.
Chronic IH-evoked cardio-respiratory responses are absent in Hif-1alpha+/- mice, and hypertension elicited by chronic IH is absent in mice lacking NFAT3c.
Study on sildenafil combined with inhalational nitric oxide therapy on the curative effects and serum levels of HIF-1α, ET-1, and calcium in neonatal pulmonary hypertension.
Dysregulation of HIF-1- and HIF-2-mediated transcription leads to imbalance of pro-oxidant and anti-oxidant enzyme gene expression resulting in increased reactive oxygen species (ROS) generation in the chemosensory reflex which is central for developing hypertension.
Pathogenesis of pulmonary hypertension is complex and involves activation of the transcription factor, hypoxia-inducible factor-1 (HIF-1) that shifts cellular metabolism from aerobic respiration to glycolysis, in part, by increasing the expression of its downstream target pyruvate dehydrogenase kinase-1 (PDK-1), thereby promoting a proliferative, apoptosis-resistant phenotype in pulmonary vascular cells.
Furthermore, HIF-1α mRNA and protein expression in Group B was significantly elevated compared with Group A. E2 and 2ME intervention significantly attenuated the aforementioned parameter changes, suggesting that E2 and 2ME partially ameliorate hypoxic pulmonary hypertension.