Alpha Omega Alpha Honor Medical Society

2012 Research Abstract

The Effect of Aging in the Heterozygous Connexin 40 Murine Model

Investigators: Satara A. Brown, MSIV, Mary S Rackley, BS, Terrence X. O’Brien, MD, Medical University of South Carolina, Charleston, SC

Mentor: Terrence X. O'Brien, MD, Medical University of South Carolina, Charleston, South Carolina

Introduction: With the increasing number of senior citizens, cardiovascular disease becomes more and more important as it is a leading cause of death in this age group. Earlier studies suggest that decrease in gap junction Connexin (Cx) 43 expression and subsequent increased collagen content may cause increased arrythmogenicity. However, these studies were conducted in a pressure-overload hypertrophy model using transverse aortic constriction (TAC). In this study, we examine the effect of aging on ventricular fibrosis in a transgenic model wherein one Cx40 allele is replaced with enhanced green fluorescence protein (EGFP). Since Cx40 is found in cardiomyocytes of the peripheral cardiac conduction system in the ventricles, this provides an opportunity to examine the long-term effect of the Cx40 heterozygous state. The same phenomena may be occurring in the aging population due to physiologic effects opposed to pathologic defects. We hypothesize that compared to young murine animals, aged animals will have increased fibrillar collagen deposition, which may be affected by the heterozygous Cx40 genetic background, and decreased Cx40 expression in cardiomyocytes.

Methods: Wild type and Cx40EGFP/+ mice were studied. Twelve senile mice between the ages of 22 and 27 months and six control mice between the ages of 3 and 10 months were utilized. Picrosirus red staining, polarized light imaging, and SigmaScan Pro 5 analysis for fibrillar collagen were performed. Immunofluorescence staining and imaging for Cx40 expression were also conducted.

Results: On average, fibrillar collagen was increased in aged animals compared to young, control animals. Mean collagen area increased from 0.176% to 0.527% (p=0.001) for wild type animals. For Cx40EGFP/+ animals, mean collagen area increased from 0.190% to 0.472% (p=0.025). There was not a major difference in collagen deposition between wild type and Cx40 aged animals. Immunofluorescence staining and analysis of Cx40 expression was unsuccessful.

Conclusion: Increased collagen deposition has been shown to cause arrhythmias and left ventricular hypertrophy in various pathologic models. In this study, it has been concluded that collagen deposition is increased in physiologically aged animals despite the Cx40 heterozygous genotype. Therefore, changes in cardiac function may be due to age-related changes in the cardiac tissue and not necessarily pathologic conditions. Further studies should be conducted utilizing an antigen capture protocol in order to study Cx40 expression with paraffin sections.

Updated on July 25, 2013.

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