scholarly journals Inhibition of heat shock protein 90 improves pulmonary arteriole remodeling in pulmonary arterial hypertension

Oncotarget ◽  
2016 ◽  
Vol 7 (34) ◽  
pp. 54263-54273 ◽  
Author(s):  
Guo-Kun Wang ◽  
Song-Hua Li ◽  
Zhi-Min Zhao ◽  
Su-Xuan Liu ◽  
Guan-Xin Zhang ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Arterial Hypertension ◽  
Heat Shock Protein 90 ◽  
Pulmonary Arteriole ◽  
Pulmonary Arterial

Abstract 14331: Role for HDAC6 in Pulmonary Arterial Hypertension

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Sophie Chabot ◽  
Grégoire Ruffenach ◽  
Sandra Breuils-Bonnet ◽  
Eve Tremblay ◽  
Olivier Boucherat ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Therapeutic Potential ◽  
Annexin V ◽  
Heat Shock Protein 90 ◽  
Scratch Test ◽  
Histone Deacetylase 6 ◽  
Apoptosis Resistance ◽  
Hsp90 Inhibition ◽  
Pulmonary Arterial

Background: Pulmonary arterial smooth muscle cells (PASMCs) from pulmonary arterial hypertension (PAH) patients exhibit a pro-proliferative, pro-migratory and anti-apoptotic phenotype mediated, at least in part, by survivin overexpression, leading to the development of progressive pulmonary artery (PA) remodeling. This results in right ventricle (RV) hypertrophy and failure. For many years, the cytoplasmic class IIb histone deacetylase 6 (HDAC6), which mainly functions as a α-tubulin deacetylase has been understudied. Several cancer studies have demonstrated that HDAC6 cooperates with the Heat Shock Protein 90 (HSP90) and regulates many signaling pathways involved in cancer and PAH development. In the cardiovascular field, HDAC6 upregulation has been associated with heart failure. We hypothesized that specific HDAC6 inhibition corrects the abnormal phenotype of PAH-PASMCs and improves RV function. Method/Results: Using a multidisciplinary and translational approach, we demonstrated that both HDAC6 and HSP90 are upregulated (Wb; p<0.01) in the lungs, distal PAs, and PASMCs from PAH patients (n=5) compared to controls (n=5). HDAC6 inhibition using Tubastatin A dose-dependently increased α-tubulin acetylation and decreased PAH-PASMC migration (scratch test; p<0.05), apoptosis resistance (Annexin-V; p<0.05) and proliferation (Ki67; p<0.01). Tubastatin A also reduced the expression of survivin in PAH-PASMCs (Wb). Similar effects were observed after HSP90 inhibition with AT13387, which also reduced HDAC6 expression in PAH-PASMCs (Wb) suggesting that a HSP90-dependent mechanism may account for HDAC6 upregulation. Within the heart, HDAC6 was exclusively expressed in human decompensated RV from PAH patients (n=5) and not in control RV (Wb, p<0.01). Conclusion: We provide evidence that HSP90 and HDAC6 are upregulated in human PAH and contribute to the proliferative, migratory and anti-apoptotic phenotype of PAH-PASMCs. Moreover, HDAC6 is specifically increased in the RV of PAH patients, suggesting that specific HDAC6 inhibition may represent a novel and attractive target in PAH for the treatment of both PA remodeling and RV failure. The therapeutic potential of HDAC6 inhibition in a PAH rat model is currently under investigation.

scholarly journals Baicalin Attenuates Hypoxia-Induced Pulmonary Arterial Hypertension to Improve Hypoxic Cor Pulmonale by Reducing the Activity of the p38 MAPK Signaling Pathway and MMP-9

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Shuangquan Yan ◽  
Yiran Wang ◽  
Panpan Liu ◽  
Ali Chen ◽  
Mayun Chen ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
P38 Mapk ◽  
Ventricular Remodeling ◽  
Cor Pulmonale ◽  
Pulmonary Arteriole ◽  
Tissue Homogenates ◽  
Pulmonary Arterial ◽  
Right Ventricular Remodeling

Baicalin has a protective effect on hypoxia-induced pulmonary hypertension in rats, but the mechanism of this effect remains unclear. Thus, investigating the potential mechanism of this effect was the aim of the present study. Model rats that display hypoxic pulmonary hypertension and cor pulmonale under control conditions were successfully generated. We measured a series of indicators to observe the levels of pulmonary arterial hypertension, pulmonary arteriole remodeling, and right ventricular remodeling. We assessed the activation of p38 mitogen-activated protein kinase (MAPK) in the pulmonary arteriole walls and pulmonary tissue homogenates using immunohistochemistry and western blot analyses, respectively. The matrix metalloproteinase- (MMP-) 9 protein and mRNA levels in the pulmonary arteriole walls were measured using immunohistochemistry and in situ hybridization. Our results demonstrated that baicalin not only reduced p38 MAPK activation in both the pulmonary arteriole walls and tissue homogenates but also downregulated the protein and mRNA expression levels of MMP-9 in the pulmonary arteriole walls. This downregulation was accompanied by the attenuation of pulmonary hypertension, arteriole remodeling, and right ventricular remodeling. These results suggest that baicalin may attenuate pulmonary hypertension and cor pulmonale, which are induced by chronic hypoxia, by downregulating the p38 MAPK/MMP-9 pathway.

scholarly journals Clinical application of pulmonary vascular resistance in patients with pulmonary arterial hypertension

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jianying Deng
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Clinical Application ◽  
Vascular Resistance ◽  
Right Heart Failure ◽  
Pulmonary Vascular Disease ◽  
Right Heart ◽  
Pulmonary Arteriole ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension is a type of malignant pulmonary vascular disease, which is mainly caused by the increase of pulmonary vascular resistance due to the pathological changes of the pulmonary arteriole itself, which eventually leads to right heart failure and death. As one of the diagnostic indicators of hemodynamics, pulmonary vascular resistance plays an irreplaceable role in the pathophysiology, diagnosis and treatment of pulmonary arterial hypertension. It provides more references for the evaluation of pulmonary arterial hypertension patients. This article summarizes the clinical application of pulmonary vascular resistance in patients with pulmonary arterial hypertension.

Glycyrrhizin effects rat hepatocytes via the reduction of heat shock protein 90 expression

2001 ◽  
Vol 120 (5) ◽  
pp. A357-A357
Author(s):  
T YOH ◽  
T NAKASHIMA ◽  
Y SUMIDA ◽  
Y KAKISAKA ◽  
H ISHIKAWA ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Heat Shock Protein 90 ◽  
Rat Hepatocytes
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