ArticleCardiovascular research2016
Modulators of right ventricular apoptosis and contractility in a rat model of pulmonary hypertension.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The trial behind it
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Who cites it
22 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Pulmonary Hypertension and Right Ventricle: A Pathophysiological Insight.Clinical Medicine Insights. Cardiology · 2024Review
- M-type pyruvate kinase 2 (PKM2) tetramerization alleviates the progression of right ventricle failure by regulating oxidative stress and mitochondrial dynamics.Journal of translational medicine · 2023Article
- The mechanism of programmed death and endoplasmic reticulum stress in pulmonary hypertension.Cell death discovery · 2023Review
- Potential Roles of Metals in the Pathogenesis of Pulmonary and Systemic Hypertension.International journal of biological sciences · 2023Review
- Xinyang Tablet attenuates chronic hypoxia-induced right ventricular remodeling via inhibiting cardiomyocytes apoptosis.Chinese medicine · 2022Article
- Targeting peptidyl-prolyl isomerase 1 in experimental pulmonary arterial hypertension.The European respiratory journal · 2022Article
- Complications and management of functional single ventricle patients with Fontan circulation: From surgeon's point of view.Frontiers in cardiovascular medicine · 2022Review
- Distinct time courses and mechanics of right ventricular hypertrophy and diastolic stiffening in a male rat model of pulmonary arterial hypertension.American journal of physiology. Heart and circulatory physiology · 2021Article
- miR-29a-3p/THBS2 Axis Regulates PAH-Induced Cardiac Fibrosis.International journal of molecular sciences · 2021Article
- Article
- Morphological and Functional Characteristics of Animal Models of Myocardial Fibrosis Induced by Pressure Overload.International journal of hypertension · 2020Review
- Nature's right ventricle-limited by design.Journal of thoracic disease · 2019Article
- EXPRESS: Right Heart in Pulmonary Hypertension: From Adaptation to Failure.Pulmonary circulation · 2019Article
- Ultrastructural Changes of the Right Ventricular Myocytes in Pulmonary Arterial Hypertension.Journal of the American Heart Association · 2019Article
- Article
- Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension.Korean circulation journal · 2018Article
- Redox Biology of Right-Sided Heart Failure.Antioxidants (Basel, Switzerland) · 2018Review
- Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions.Circulation research · 2018Article
- Transglutaminase 2 in pulmonary and cardiac tissue remodeling in experimental pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
aimsRight ventricular (RV) failure is the major cause of death among patients with pulmonary arterial hypertension (PAH). However, the mechanism of RV failure has not been defined. METHODS AND
resultsThis study examined mechanisms and consequences of RV myocyte apoptosis and fibrosis in response to PAH. Rats were injected with SU5416 (vascular endothelial growth factor inhibitor), followed by hypoxia for 3 weeks, and subsequently maintained in normoxia for 2, 5, or 14 weeks (5-, 8-, and 17-week time points after the SU5416 injection, respectively). RV systolic pressure (RVSP) was elevated to >70 mmHg at 5-week time point, and this pressure was sustained thereafter. Significant RV myocyte apoptosis and fibrosis were observed at 8- and 17-week time points. Apoptosis was associated with downregulated Bcl-xL (anti-apoptotic protein), downregulated GATA4 (transcriptional regulator of Bcl-xL), and upregulated p53 (negative regulator of GATA4 gene transcription). PAH-mediated RV apoptosis and fibrosis were attenuated in p53 knock-out rats. Despite the major loss of cardiomyocytes, RV contractility was enhanced, suggesting that the remaining myocytes can perform improved contractile functions. Improved RV contractility is associated with the increased expression of contractile and sarcoplasmic reticulum Ca(2+) uptake proteins. In contrast, the expression of calsequestrin 2 (CSQ2) was downregulated. The siRNA knockdown of CSQ2 improved RV contractility and increased the expression of contractile and Ca(2+) uptake proteins.
conclusionThese results suggest that RV decompensation is associated with the death of cardiomyocytes, resulting in fibrosis. However, the remaining myocytes are capable of sustaining RV contractility through the mechanism that involves CSQ2.
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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.