Expression of placenta growth factor, soluble fms-like tyrosine kinase-1, metal-responsive transcription factor-1, heme oxygenase 1 and hypoxia inducible factor-1α mRNAs in pre-eclampsia placenta and the effect of pre-eclampsia sera on their expression of

2014 ◽  
Vol 40 (10) ◽  
pp. 2095-2103 ◽  
Author(s):  
Aki Maebayashi Asanuma ◽  
Tatsuo Yamamoto ◽  
Hiromitu Azuma ◽  
Erina Kato ◽  
Noriko Yamamoto ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Placenta Growth Factor ◽  
Hypoxia Inducible Factor 1Α ◽  
Transcription Factor 1

scholarly journals Placenta growth factor augments endothelin-1 and endothelin-B receptor expression via hypoxia-inducible factor-1α

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 856-865 ◽  
Author(s):  
Nitin Patel ◽  
Caryn S. Gonsalves ◽  
Punam Malik ◽  
Vijay K. Kalra
Keyword(s):  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Receptor Expression ◽  
Placenta Growth Factor ◽  
Promoter Regions ◽  
Endothelin B Receptor ◽  
Endothelin 1 ◽  
Hypoxia Inducible Factor 1Α ◽  
Endothelin B ◽  
Potent Vasoconstrictor

Abstract Pulmonary hypertension (PHT) develops in sickle cell disease (SCD) and is associated with high mortality. We previously showed that erythroid cells produce placenta growth factor (PlGF), which activates monocytes to induce proinflammatory cytochemokines, contributing to the baseline inflammation and severity in SCD. In this study, we observed that PlGF increased expression of endothelin-1 (ET-1) and endothelin-B receptor (ET-BR) from human pulmonary microvascular endothelial cells (HPMVECs) and monocytes, respectively. PlGF-mediated ET-1 and ET-BR expression occurred via activation of PI-3 kinase, reactive oxygen species and hypoxia inducible factor-1α (HIF-1α). PlGF increased binding of HIF-1α to the ET-1 and ET-BR promoters; this effect was abrogated with mutation of hypoxia response elements in the promoter regions and HIF-1α siRNA and confirmed by chromatin immunoprecipitation analysis. Furthermore, PlGF-mediated ET-1 release from HPMVECs and ET-BR expression in monocytes creates a PlGF–ET-1–ET-BR loop, leading to increased expression of MCP-1 and IL-8. Our studies show that PlGF-induced expression of the potent vasoconstrictor ET-1 and its cognate ET-BR receptor occur via activation of HIF-1α, independent of hypoxia. PlGF levels are intrinsically elevated from the increased red cell turnover in SCD and in other chronic anemia (eg, thalassemia) and may contribute to inflammation and PHT seen in these diseases.

scholarly journals Hmox1 (Heme Oxygenase-1) Protects Against Ischemia-Mediated Injury via Stabilization of HIF-1α (Hypoxia-Inducible Factor-1α)

2020 ◽  
Author(s):  
Louise L. Dunn ◽  
Stephanie M.Y. Kong ◽  
Sergey Tumanov ◽  
Weiyu Chen ◽  
James Cantley ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Carbon Monoxide ◽  
Blood Flow ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Ischemic Injury ◽  
Heme Oxygenase 1 ◽  
Wild Type ◽  
Tissue Necrosis ◽  
Hypoxia Inducible Factor 1Α

Objective: Hmox1 (heme oxygenase-1) is a stress-induced enzyme that catalyzes the degradation of heme to carbon monoxide, iron, and biliverdin. Induction of Hmox1 and its products protect against cardiovascular disease, including ischemic injury. Hmox1 is also a downstream target of the transcription factor HIF-1α (hypoxia-inducible factor-1α), a key regulator of the body’s response to hypoxia. However, the mechanisms by which Hmox1 confers protection against ischemia-mediated injury remain to be fully understood. Approach and Results: Hmox1 deficient ( Hmox1 –/– ) mice had impaired blood flow recovery with severe tissue necrosis and autoamputation following unilateral hindlimb ischemia. Autoamputation preceded the return of blood flow, and bone marrow transfer from littermate wild-type mice failed to prevent tissue injury and autoamputation. In wild-type mice, ischemia-induced expression of Hmox1 in skeletal muscle occurred before stabilization of HIF-1α. Moreover, HIF-1α stabilization and glucose utilization were impaired in Hmox1 –/– mice compared with wild-type mice. Experiments exposing dermal fibroblasts to hypoxia (1% O 2 ) recapitulated these key findings. Metabolomics analyses indicated a failure of Hmox1 –/– mice to adapt cellular energy reprogramming in response to ischemia. Prolyl-4-hydroxylase inhibition stabilized HIF-1α in Hmox1 –/– fibroblasts and ischemic skeletal muscle, decreased tissue necrosis and autoamputation, and restored cellular metabolism to that of wild-type mice. Mechanistic studies showed that carbon monoxide stabilized HIF-1α in Hmox1 –/– fibroblasts in response to hypoxia. Conclusions: Our findings suggest that Hmox1 acts both downstream and upstream of HIF-1α, and that stabilization of HIF-1α contributes to Hmox1’s protection against ischemic injury independent of neovascularization.

scholarly journals NF-κB contributes to transcription of placenta growth factor and interacts with metal responsive transcription factor-1 in hypoxic human cells

2006 ◽  
Vol 387 (1) ◽  
Author(s):  
Mirjam Cramer ◽  
Ivana Nagy ◽  
Brian J. Murphy ◽  
Max Gassmann ◽  
Michael O. Hottiger ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Growth Factor ◽  
Human Cells ◽  
Placenta Growth Factor ◽  
Transcription Factor 1

Expression of heme oxygenase-1, hypoxia inducible factor-1α, and ubiquitin in peripheral inflammatory cells from patients with coronary heart disease

2009 ◽  
Vol 47 (3) ◽  
Author(s):  
Song-Ming Chen ◽  
Yu-Guang Li ◽  
Dong-Ming Wang ◽  
Guo-Hong Zhang ◽  
Chun-Jiang Tan
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Angina Pectoris ◽  
Protein Expression ◽  
Mrna Expression ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Hypoxia Inducible Factor 1Α ◽  
Monocytes And Lymphocytes

Abstract: The increased expression of heme oxygenase-1 content, a stress-response protein, directly correlates with the incidence of coronary heart disease. Down-regulation of hypoxia inducible factor-1α activity, a major downstream effector of the signaling pathways activated by hypoxia, increases cell survival after hypoxia. The ubiquitin system, a non-lysosomal pathway of protein degradation, is involved in processes of coronary heart disease. The aim of this study was to investigate the expression of heme oxygenase-1, hypoxia inducible factor-1α, and ubiquitin in both monocytes and lymphocytes isolated from patients at the mRNA and protein levels in different stages of coronary heart disease and their possible correlation.: A total of 90 patients with coronary heart disease (30 acute myocardial infarction, 30 unstable angina pectoris, and 30 stable angina pectoris) were selected, and 30 cases with normal coronary artery served as controls. The mRNA and protein expression of heme oxygenase-1, hypoxia inducible factor-1α, and ubiquitin in monocytes and lymphocytes were examined by semi-quantitative reverse transcriptase polymerase chain reaction and Western blotting, respectively.: The mRNA expression of heme oxygenase-1 and ubiquitin was associated with the severity of coronary heart disease (p<0.05). There was no significant difference in hypoxia inducible factor-1α mRNA expression between the coronary heart disease patients and controls. The protein expression of heme oxygenase-1, hypoxia inducible factor-1α, and ubiquitin was significantly stronger in patients with coronary heart disease than in controls, and the expression levels increased with the severity of the disease. There was a positive association between heme oxygenase-1 and hypoxia inducible factor-1α and ubiquitin, antioxidative therapy with adrenergic receptor blocker, angiotensin-converting enzyme inhibitor or statins up-regulated the expression of heme oxygenase-1 and hypoxia inducible factor-1α.: These data suggest that heme oxygenase-1, hypoxia inducible factor-1α, and ubiquitin are involved in the development and progression of coronary heart disease and thus may be useful biomarkers for coronary heart disease.Clin Chem Lab Med 2009;47:327–33.

Combined Gene Therapy with Hypoxia-Inducible Factor-1α and Heme Oxygenase-1 for Therapeutic Angiogenesis

2011 ◽  
Vol 17 (7-8) ◽  
pp. 915-926 ◽  
Author(s):  
Suk Ho Bhang ◽  
Ju Hee Kim ◽  
Hee Seok Yang ◽  
Wan-Geun La ◽  
Tae-Jin Lee ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Therapeutic Angiogenesis ◽  
Heme Oxygenase 1 ◽  
Hypoxia Inducible Factor 1Α ◽  
Combined Gene Therapy

scholarly journals Liraglutide via Activation of AMP-Activated Protein Kinase-Hypoxia Inducible Factor-1α-Heme Oxygenase-1 Signaling Promotes Wound Healing by Preventing Endothelial Dysfunction in Diabetic Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Huiya Huang ◽  
Linlin Wang ◽  
Fanyu Qian ◽  
Xiong Chen ◽  
Haiping Zhu ◽  
...  
Keyword(s):  
Wound Healing ◽  
Protein Kinase ◽  
Endothelial Dysfunction ◽  
Heme Oxygenase ◽  
Hypoxia Inducible Factor ◽  
Heme Oxygenase 1 ◽  
Diabetic Wound ◽  
Hypoxia Inducible Factor 1Α ◽  
Diabetic Wound Healing ◽  
Amp Activated Protein Kinase

Background/Aims: Diabetic foot ulcers (DFUs) present a major challenge in clinical practice, and hyperglycemia-induced angiogenesis disturbance and endothelial dysfunction likely exacerbate DFUs. The long-acting glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira) is a potential activator of AMP-activated protein kinase (AMPK) that appears to enhance endothelial function and have substantial pro-angiogenesis and antioxidant stress effects. Therefore, in this study, we aimed to investigate whether the protective role of Lira in diabetic wound healing acts against the mechanisms underlying hyperglycemia-induced endothelial dysfunction and angiogenesis disturbance.Methods: Accordingly, db/db mice were assessed after receiving subcutaneous Lira injections. We also cultured human umbilical vein endothelial cells (HUVECs) in either normal or high glucose (5.5 or 33 mM glucose, respectively) medium with or without Lira for 72 h.Results: An obvious inhibition of hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance was observed; follow by a promotion of diabetic wound healing under Lira treatment combined with restored hyperglycemia-impaired AMPK signaling pathway activity. AMPKα1/2 siRNA and Compound C (Cpd C), an inhibitor of AMPK, abolished both Lira-mediated endothelial protection and pro-angiogenesis action, as well as the diabetic wound healing promoted by Lira. Furthermore, hypoxia inducible factor-1α (Hif-1α; transcription factors of AMPK substrates) knockdown in HUVECs and db/db mice demonstrated that Lira activated AMPK to prevent hyperglycemia-triggered endothelial dysfunction and angiogenesis disturbance, with a subsequent promotion of diabetic wound healing that was Hif-1α–heme oxygenase-1 (HO-1) axis-dependent. Taken together, these findings reveal that the promotion of diabetic wound healing by Lira occurs via its AMPK-dependent endothelial protection and pro-angiogenic effects, which are regulated by the Hif-1α–HO-1 axis.

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