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Calpain Inhibition Decreases Myocardial Fibrosis in Chronically Ischemic Hypercholesterolemic Swine (Record no. 1708)

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Personal name Potz, Brittany A.
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9 (RLIN) 942
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Title Calpain Inhibition Decreases Myocardial Fibrosis in Chronically Ischemic Hypercholesterolemic Swine
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Date of publication, distribution, etc. 2020-03-29.
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General note /pmc/articles/PMC7529741/
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General note /pubmed/32359903
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Summary, etc. OBJECTIVES: Calpain 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. METHODS: Yorkshire 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. RESULTS: In the setting of hypercholesterolemia and chronic myocardial ischemia, CI decreased the expression of collagen in ischemic and non-ischemic 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. CONCLUSIONS: Calpain inhibition may be a beneficial medical therapy to decrease collagen formation in patients with coronary artery disease and associated co-morbidities.
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Personal name Sabe, Ashraf A.
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9 (RLIN) 943
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Personal name Sabe, Sharif A.
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9 (RLIN) 944
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Personal name Lawandy, Isabella J.
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9 (RLIN) 945
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Personal name Abid, M. Ruhul
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Personal name Clements, Richard T.
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9 (RLIN) 947
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Personal name Sellke, Frank W.
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9 (RLIN) 948
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Note J Thorac Cardiovasc Surg
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Uniform Resource Identifier <a href="http://dx.doi.org/10.1016/j.jtcvs.2019.11.150">http://dx.doi.org/10.1016/j.jtcvs.2019.11.150</a>
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