Cardiovascular disease is the result of complicated pathophysiological processes in the tissues that make up the blood vessels and heart. Heat shock protein 90 (HSP90) can interact with 10% of the proteome and is the most widely studied molecular chaperone in recent years. HSP90 is extensively involved in the regulation of protein folding and intracellular protein stability, making HSP90 a hopeful target for the treatment of multiple cardiovascular diseases. Numerous client proteins of HSP90 have been identified in known cardiac disease pathways, including MAPK signaling, PI3K/AKT (PKB)/mTOR, and TNF-α signaling. Therefore, these pathways can be controlled by regulating HSP90. Among them, the activity of HSP90 can be regulated via numerous inhibitors. In this review, first, we will discuss the function of HSP90 and its role in pathological pathways. In addition, HSP90 plays a significant role in most cardiovascular diseases, including hypertension, pulmonary venous hypertension, atherosclerosis, and heart failure; next we will focus on this part. Finally, we will summarize the currently known HSP90 inhibitors and their potential in the treatment of heart disease.
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http://dx.doi.org/10.3390/cells11213444 | DOI Listing |
Circ Genom Precis Med
January 2025
CARIM School for Cardiovascular Diseases (A.I., S.Z., J.W., B.B., H.J.G.M.C., B.H., M.K., S.V., U.S., M.S.), Maastricht University, the Netherlands.
Background: Transcriptional dysregulation, possibly affected by genetic variation, contributes to disease development. Due to dissimilarities in development, function, and remodeling during disease progression, transcriptional differences between the left atrial (LA) and right atrial (RA) may provide insight into diseases such as atrial fibrillation.
Methods: Lateral differences in atrial transcription were evaluated in CATCH ME (Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly) using a 2-stage discovery and replication design.
Circ Res
January 2025
Key Laboratory of Drug Targets and Translational Medicine for Cardio-cerebrovascular Diseases, Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Jiangsu, China (X.T., X.L., X.S., Y. Zhang, Y. Zu, Q.F., L.H., S.S., F.C., L.X., Y.J.).
Background: The decrease in S-nitrosoglutathione reductase (GSNOR) leads to an elevation of S-nitrosylation, thereby exacerbating the progression of cardiomyopathy in response to hemodynamic stress. However, the mechanisms under GSNOR decrease remain unclear. Here, we identify NEDD4 (neuronal precursor cell expressed developmentally downregulated 4) as a novel molecule that plays a crucial role in the pathogenesis of pressure overload-induced cardiac hypertrophy, by modulating GSNOR levels, thereby demonstrating significant therapeutic potential.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
Department of Pediatrics, Division of Pediatric Infectious Diseases, Guerin Children's, Cedars-Sinai Medical Center, Los Angeles, CA.(P.K.J., M.A., M.N.R.).
The intestinal microbiota influences many host biological processes, including metabolism, intestinal barrier functions, and immune responses in the gut and distant organs. Alterations in its composition have been associated with the development of inflammatory disorders and cardiovascular diseases, including Kawasaki disease (KD). KD is an acute pediatric vasculitis of unknown etiology and the leading cause of acquired heart disease in children in the United States.
View Article and Find Full Text PDFArterioscler Thromb Vasc Biol
January 2025
Metabolic and Immune Diseases Department, Biomedical Research Institute Sols-Morreale (IIBM), National Research Council (CSIC), Autonoma University of Madrid, Spain (T.A.-G., S.M.-T., R.C.-M., S.U.-B., S.M.-P.).
Background: Hypoxia is associated with the onset of cardiovascular diseases including cardiac hypertrophy and pulmonary hypertension. HIF2 (hypoxia-inducible factor 2) signaling in the endothelium mediates pulmonary arterial remodeling and subsequent elevation of the right ventricular systolic pressure during chronic hypoxia. Thus, novel therapeutic opportunities for pulmonary hypertension based on specific HIF2 inhibitors have been proposed.
View Article and Find Full Text PDFCirc Genom Precis Med
January 2025
Department of Medicine, Division of Cardiology (M.P., N.J.P., N.P.S.), Duke University, Durham, NC.
Background: Established risk models may not be applicable to patients at higher cardiovascular risk with a measured Lp(a) (lipoprotein[a]) level, a causal risk factor for atherosclerotic cardiovascular disease.
Methods: This was a model development study. The data source was the Nashville Biosciences Lp(a) data set, which includes clinical data from the Vanderbilt University Health System.
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