New Insights Into Heat Shock Protein 90 in the Pathogenesis of Pulmonary Arterial Hypertension
Open Access
- 15 September 2020
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Physiology
Abstract
Pulmonary arterial hypertension (PAH) is a multifactorial and progressive disorder. This disease is characterized by vasoconstriction and vascular remodeling, which results in increased pulmonary artery pressure and pulmonary vascular resistance. Although extensive studies have been carried out to understand the etiology, it is still unclear what intracellular factors contribute and integrate these pathological features. Heat shock protein 90 (Hsp90), a ubiquitous and essential molecular chaperone, is involved in the maturation of many proteins. An increasing number of studies have revealed direct connections between abnormal Hsp90 expression and cellular factors related to PAH, such as soluble guanylate cyclase and AMP-activated protein kinase. These studies suggest that the Hsp90 regulatory network is a major predictor of poor outcomes, providing novel insights into the pathogenesis of PAH. For the first time, this review summarizes the interplay between the Hsp90 dysregulation and different proteins involved in PAH development, shedding novel insights into the intrinsic pathogenesis and potentially novel therapeutic strategies for this devastating disease.Funding Information
- National Natural Science Foundation of China
This publication has 97 references indexed in Scilit:
- Pulmonary Arterial Hypertension: Combination Therapy in PracticeAmerican Journal of Cardiovascular Drugs, 2018
- Mitochondrial HSP90 Accumulation Promotes Vascular Remodeling in Pulmonary Arterial HypertensionAmerican Journal of Respiratory and Critical Care Medicine, 2018
- Differential effects of heat shock protein 90 and serine 1179 phosphorylation on endothelial nitric oxide synthase activity and on its cofactorsPLOS ONE, 2017
- The cancer theory of pulmonary arterial hypertensionPulmonary Circulation, 2017
- Conformational processing of oncogenic v-Src kinase by the molecular chaperone Hsp90Proceedings of the National Academy of Sciences of the United States of America, 2015
- Endothelial Nitric Oxide Synthase Dimerization Is Regulated by Heat Shock Protein 90 Rather than by PhosphorylationPLOS ONE, 2014
- Predicting Survival in Pulmonary Arterial HypertensionCirculation, 2010
- Crystal structure of an Hsp90–nucleotide–p23/Sba1 closed chaperone complexNature, 2006
- Endothelial Dysfunction in Pulmonary HypertensionCirculation, 2004
- Heat Shock Protein 90 in Endothelial Nitric Oxide Synthase SignalingCirculation Research, 2002