ArticleAmerican journal of physiology. Heart and circulatory physiology2013
Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure.
Article in American journal of physiology. Heart and circulatory physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- PKA-Mediated Proteasome Activation Protects Against Cardiac Remodeling and Heart Failure During Systolic Overload.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- Chronic therapy with α1A-adrenergic agonist reverses RV failure and mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Not Just PA28γ: What We Know About the Role of PA28αβ in Carcinogenesis.Biomolecules · 2025Review
- Promoting proteostasis by cAMP/PKA and cGMP/PKG.Trends in molecular medicine · 2025Review
- The role of deubiquitinases in cardiac disease.Expert reviews in molecular medicine · 2024Review
- Genetic insights into the effect of trace elements on cardiovascular diseases: multi-omics Mendelian randomization combined with linkage disequilibrium score regression analysis.Frontiers in immunology · 2024Article
- Pivotal Role of Ubiquitin Carboxyl-Terminal Hydrolase L1 (UCHL1) in Uterine Leiomyoma.Biomolecules · 2023Article
- Ubiquitin Carboxyl-Terminal Hydrolase L1 of Cardiomyocytes Promotes Macroautophagy and Proteostasis and Protects Against Post-myocardial Infarction Cardiac Remodeling and Heart Failure.Frontiers in cardiovascular medicine · 2022Article
- Exploring Functional Differences between the Right and Left Ventricles to Better Understand Right Ventricular Dysfunction.Oxidative medicine and cellular longevity · 2021Review
- Thyroid Hormone Plays an Important Role in Cardiac Function: From Bench to Bedside.Frontiers in physiology · 2021Review
- Treatment Targets for Right Ventricular Dysfunction in Pulmonary Arterial Hypertension.JACC. Basic to translational science · 2020Review
- Blockage of UCHL1 activity attenuates cardiac remodeling in spontaneously hypertensive rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Article
- The Calcineurin-TFEB-p62 Pathway Mediates the Activation of Cardiac Macroautophagy by Proteasomal Malfunction.Circulation research · 2020Article
- Priming the Proteasome to Protect against Proteotoxicity.Trends in molecular medicine · 2020Review
- Targeting Protein Kinase G to Treat Cardiac Proteotoxicity.Frontiers in physiology · 2020Review
- Cellular Protein Quality Control in Diabetic Cardiomyopathy: From Bench to Bedside.Frontiers in cardiovascular medicine · 2020Review
- PDE1 inhibition facilitates proteasomal degradation of misfolded proteins and protects against cardiac proteinopathy.Science advances · 2019Article
- Highly Dynamic Changes in the Activity and Regulation of Macroautophagy in Hearts Subjected to Increased Proteotoxic Stress.Frontiers in physiology · 2019Article
- Reversal of right ventricular failure by chronic αAmerican journal of physiology. Heart and circulatory physiology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Alterations in the ubiquitin-proteasome system (UPS) have been described in left ventricular hypertrophy and failure, although results have been inconsistent. The role of the UPS in right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) is unknown. Given the greater percent increase in RV mass associated with RV afterload stress, as present in many congenital heart lesions, we hypothesized that alterations in the UPS could play an important role in RVH/RVF. UPS expression and activity were measured in the RV from mice with RVH/RVF secondary to pulmonary artery constriction (PAC). Epoxomicin and MG132 were used to inhibit the proteasome, and overexpression of the 11S PA28α subunit was used to activate the proteasome. PAC mice developed RVH (109.3% increase in RV weight to body weight), RV dilation with septal shift, RV dysfunction, and clinical RVF. Proteasomal function (26S β₅ chymotrypsin-like activity) was decreased 26% (P < 0.05). Protein expression of 19S subunit Rpt5 (P < 0.05), UCHL1 deubiquitinase (P < 0.0001), and Smurf1 E3 ubiquitin ligase (P < 0.01) were increased, as were polyubiquitinated proteins (P < 0.05) and free-ubiquitins (P = 0.05). Pro-apoptotic Bax was increased (P < 0.0001), whereas anti-apoptotic Bcl-2 decreased (P < 0.05), resulting in a sixfold increase in the Bax/Bcl-2 ratio. Proteasomal inhibition did not accelerate RVF. However, proteasome enhancement by cardiac-specific proteasome overexpression partially improved survival. Proteasome activity is decreased in RVH/RVF, associated with upregulation of key UPS regulators and pro-apoptotic signaling. Enhancement of proteasome function partially attenuates RVF, suggesting that UPS dysfunction contributes to RVF.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.