ArticleThe Journal of thoracic and cardiovascular surgery2022
Calpain inhibition decreases myocardial fibrosis in chronically ischemic hypercholesterolemic swine.
Article in The Journal of thoracic and cardiovascular surgery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Unraveling the pleiotropic effects of CCR2-dependent signal transduction in fibrosis development.Theranostics · 2026Review
- Review
- Calpain inhibition as a novel therapeutic strategy for aortic dissection with acute lower extremity ischemia.Molecular medicine (Cambridge, Mass.) · 2025Observational
- Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia.Free radical biology & medicine · 2023Article
- One Billion hiPSC-Cardiomyocytes: Upscaling Engineered Cardiac Tissues to Create High Cell Density Therapies for Clinical Translation in Heart Regeneration.Bioengineering (Basel, Switzerland) · 2023Article
- Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.Frontiers in pharmacology · 2023Review
- Orai3 mediates Orai channel remodelling to activate fibroblast in pulmonary fibrosis.Journal of cellular and molecular medicine · 2022Article
- Calpains as Potential Therapeutic Targets for Myocardial Hypertrophy.International journal of molecular sciences · 2022Review
- Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing.International journal of molecular sciences · 2022Review
- Inhibiting calpain 1 and 2 in cyclin G associated kinase-knockout mice mitigates podocyte injury.JCI insight · 2020Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
objectivesCalpain activation during ischemia is known to play critical roles in myocardial remodeling. We hypothesize that calpain inhibition (CI) may serve to reverse and/or prevent fibrosis in chronically ischemic myocardium.
methodsYorkshire swine were fed a high-cholesterol diet for 4 weeks followed by placement of an ameroid constrictor on the left circumflex artery to induce myocardial ischemia. 3 weeks later, animals received either: no drug; high-cholesterol control group (CON; n = 8); low-dose CI (0.12 mg/kg; LCI, n = 9); or high-dose CI (0.25 mg/kg; HCI, n = 8). The high-cholesterol diet and CI were continued for 5 weeks, after which myocardial tissue was harvested. Tissue samples were analyzed by western blot for changes in protein content.
resultsIn the setting of hypercholesterolemia and chronic myocardial ischemia, CI decreased the expression of collagen in ischemic and nonischemic myocardial tissue. This reduced collagen content was associated with a corresponding decrease in Jak/STAT/MCP-1 signaling pathway, suggesting a role for Jak 2 signaling in calpain activity. CI also decreases the expression of focal adhesion proteins (vinculin) and stabilizes the expression of cytoskeletal and structural proteins (N-cadherin, α-fodrin, desmin, vimentin, filamin, troponin-I). CI had no significant effect on metabolic and hemodynamic parameters.
conclusionsCalpain inhibition may be a beneficial medical therapy to decrease collagen formation in patients with coronary artery disease and associated comorbidities.
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