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Calpain Inhibition Decreases Collagen Formation and Modulates Cytoskeletal Protein Expression In A Swine Model Of Chronic Myocardial Ischemia
*Brittany A Potz, *Ashraf Sabe, *Nassrene Elmadhun, Frank Sellke
Brown University, Providence, RI
Objective: We hypothesized that moderate calpain inhibition (CI) would modulate collagen formation and cytoskeletal protein expression in the ischemic and non-ischemic myocardium of hypercholesterolemic swine.
Methods: Yorkshire swine were fed a high cholesterol diet for four weeks and underwent placement of an ameroid constrictor on the left circumflex artery. Three weeks later animals received either: no drug, high cholesterol control group (HCC; 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 seven weeks, after which the pigs were euthanized and the left ventricular myocardium was harvested and analyzed via western blot and picrosirius red stain.
Results: In the ischemic and nonischemic myocardial tissue, there were significant decreases in the percentage of collagen present in the calpain-inhibited groups compared to the control. In the ischemic myocardial tissue, there were significant increases in six (of 11 cytoskeletal proteins tested) in the calpain-inhibited groups compared to the control. [Figure 2]. In the non-ischemic tissue, calpain inhibition had no effect on seven (of 11 proteins tested) and significantly decreased the expression of filamin, β Actin and β tubulin compared to the control group.
Conclusions: In the setting of hypercholesterolemia and chronic myocardial ischemia, calpain inhibition decreases collagen formation in the ischemic and nonischemic myocardial tissue. Calpain inhibition increases cytoskeletal protein expression in the ischemic myocardial tissue and has no effect or decreases the expression on cytoskeletal protein expression in the nonischemic tissue. 
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