Abstract 19177: Calpain Inhibition Stabilizes Cytoskeletal Protein Expression in Chronically Ischemic Myocardium of Hypercholestrolemic Swine
Introduction: In the setting of myocardial ischemia, calpain inhibition has been found to increase myocardial blood flow and vessel density and improve oxidative stress in myocardial tissue. Calpain inhibition may serve as a potential medical therapy for patients with coronary artery disease who are not candidates for surgical intervention.
Hypothesis: 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 4 weeks and underwent placement of an ameroid constrictor on the left circumflex artery. 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 the pigs underwent a harvest procedure.
Results: Calpain inhibition had no effect on hemodynamic measurements or metabolic parameters. In the ischemic and nonischemic myocardial tissue, there were significant decreases of collagen present in the calpain-inhibited groups compared to the control. In the ischemic myocardial tissue, calpain inhibition was associated with increased expression of α-fodrin, desmin, vimentin, filamin, N-cadherin and Troponin-I and decreased expression of α-SNAP. (Figure 1) QT-PCR proved that these changed occurred post transcriptionally.
Conclusions: In the setting of hypercholesterolemia and chronic myocardial ischemia, calpain inhibition results in decreased collagen content in ischemic and nonischemic myocardial tissue and increased cytoskeletal protein expression in the ischemic myocardial tissue. Stabilization of cystoskeletal structure provides a mechanism through which calpain inhibition may increase blood flow to chronically ischemic myocardial tissue in the setting of hypercholesterolemia.
Author Disclosures: B.A. Potz: None. S.A. Sabe: None. B.J. Braun: None. R.T. Clements: None. A. Usheva: None. F.W. Sellke: None.
- © 2016 by American Heart Association, Inc.