ArticleCirculation research2008
Targeting the calpain/calpastatin system as a new strategy to prevent cardiovascular remodeling in angiotensin II-induced hypertension.
Article in Circulation research, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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78 citing papers in PubMed, 163 citations in OpenAlex.
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- Inhibition of calpain-mediated HMGB1 alleviates cardiac inflammation and dysfunction induced by ultra-processed foods.JCI insight · 2026Article
- Using fibre photometry with a fluorescence resonance energy transfer-based biosensor to test efficacy of calpain inhibitorsBrain communications · 2026Article
- Bicuspid Aortic Valve: Old and Novel Gene Contribution to Disease Onset and Complications.Diagnostics (Basel, Switzerland) · 2025Article
- Cathepsin B in human peripheral blood lymphocytes as a peripheral biomarker for cardiac hypertrophy.Scientific reports · 2025Article
- Calpain inhibition in a transgenic model of calpastatin overexpression facilitates reversal of myocardial hypertrophy.ESC heart failure · 2025Article
- Calpain inhibition as a novel therapeutic strategy for aortic dissection with acute lower extremity ischemia.Molecular medicine (Cambridge, Mass.) · 2025Observational
- Efficacy of a cysteine protease inhibitor compared with enalapril in murine heart failure models.iScience · 2024Article
- Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.Free radical biology & medicine · 2023Article
- Cardiovascular toxicity of tyrosine kinase inhibitors during cancer treatment: Potential involvement of TRPM7.Frontiers in cardiovascular medicine · 2023Review
- The key role of Calpain in COVID-19 as a therapeutic strategy.Inflammopharmacology · 2022Review
- Calpains as mechanistic drivers and therapeutic targets for ocular disease.Trends in molecular medicine · 2022Review
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Genome-Wide Association of New-Onset Hypertension According to Renin Concentration: The Korean Genome and Epidemiology Cohort Study.Journal of cardiovascular development and disease · 2022Article
- Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.The Journal of thoracic and cardiovascular surgery · 2022Article
- Spatio-temporal regulation of calpain activity after experimental myocardial infarction in vivo.Biochemistry and biophysics reports · 2021Article
- Calpain-Mediated Mitochondrial Damage: An Emerging Mechanism Contributing to Cardiac Disease.Cells · 2021Review
- Calpastatin-Mediated Inhibition of Calpain Ameliorates Skin Scar Formation after Burn Injury.International journal of molecular sciences · 2021Article
- PAR-4/CaCardiovascular diabetology · 2021Article
- Exercise triggers CAPN1-mediated AIF truncation, inducing myocyte cell death in arrhythmogenic cardiomyopathy.Science translational medicine · 2021Article
18 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In hypertension, angiotensin (Ang) II is a critical mediator of cardiovascular remodeling, whose prominent features include myocardial and vascular media hypertrophy, perivascular inflammation, and fibrosis. The signaling pathways responsible for these alterations are not completely understood. Here, we investigated the importance of calpains, calcium-dependent cysteine proteases. We generated transgenic mice constitutively expressing high levels of calpastatin, a calpain-specific inhibitor. Chronic infusion of Ang II led to similar increases in systolic blood pressure in wild-type and transgenic mice. In contrast, compared with wild-type mice, transgenic mice displayed a marked blunting of Ang II-induced hypertrophy of left ventricle. Ang II-dependent vascular remodeling, ie, media hypertrophy and perivascular inflammation and fibrosis, was also limited in both large arteries (aorta) and small kidney arteries from transgenic mice as compared with wild type. In vitro experiments using vascular smooth muscle cells showed that calpastatin transgene expression blunted calpain activation by Ang II through epidermal growth factor receptor transactivation. In vivo and in vitro models of inflammation showed that impaired recruitment of mononuclear cells in transgenic mice was attributable to a decrease in both the release of and the chemotactic response to monocyte chemoattractant protein-1. Finally, results from collagen synthesis assay and zymography suggested that limited fibrogenesis was attributable to a decrease in collagen deposition rather than an increase in collagen degradation. These results indicate a critical role for calpains as downstream mediators in Ang II-induced cardiovascular remodeling and, thus, highlight an attractive therapeutic target.
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