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Abstract: Poster Presentations |

HEART FAILURE IN DIABETES IS ASSOCIATED WITH ALTERATIONS IN THE DYSTROPHIN GLYCOPROTEIN COMPLEX COMPOSITION AND EXPRESSION IN THE MYOCARDIUM FREE TO VIEW

Muhammad T. Gill, MD*; Kevin Rice, MS; Devashish Desai, MS; Sobia Yaqub, MD; Eric R. Blough, PhD; Paulette S. Wehner, MD, FCCP
Author and Funding Information

Marshall University School of Medicine, Huntington, WV


Chest


Chest. 2007;132(4_MeetingAbstracts):581a. doi:10.1378/chest.132.4_MeetingAbstracts.581a
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Abstract

PURPOSE: Diabetes is a major risk factor for cardiovascular disease and is associated with an increased risk of coronary artery disease and heart failure. Heart failure is more common in diabetic patients and is independent of the presence or absence of coronary artery disease. Disruption of myocardial dystrophin has been shown to cause heart failure. Dystrophin exists in the cell as part of the dystrophin glycoprotein complex (DGC). Whether development of heart failure in diabetes is associated with alterations of DGC composition or expression in the myocardium is not known.

METHODS: We compared the expression of the various components of the DGC in the hearts of lean zucker (controls) and obese zucker rats (an established model of syndrome × exhibiting type II diabetes). Immunobloting and immunohistochemical analyses were performed on cell membrane and cytosolic components of cardiomyocytes obtained from lean zucker and diabetic obese zucker (OSXZ) rats to analyze and compare the expression and localization of components of DGC.

RESULTS: Immunobloting analysis revealed markedly high cytoplasmic dystrophin content (39.95 ± 3.7%) in the OSXZ rats as compared to the control group. There was no significant difference in the membrane dystrophin component. The content of other components of the DGC complex; α-dystroglycan was 35.99 ± 2.9% and 34.74 ± 2.57% higher in the membrane and cytosolic fractions of the OSXZ hearts as compared to the controls. The cytosolic content of β-dystroglycan was 49.84 ± 6.4 % higher in the OSXZ hearts when compared to the controls while the membrane content was 28.82% higher. Immunohistochemistry revealed variable expression of dystrophin, α-dystroglycan and β-dystroglycan similar to one observed in immunoblotting.

CONCLUSION: These preliminary data suggest alterations in the composition and expression of the DGC in the hearts of normal and OSXZ rats. These differences might explain one of the mechanisms of heart failure in diabetic patients.

CLINICAL IMPLICATIONS: These preliminary findings give us an insight in understanding the underlying pathophysiologic mechanisms of heart failure in diabetic patients and might contribute towards further treatment strategies.

DISCLOSURE: Muhammad Gill, No Financial Disclosure Information; No Product/Research Disclosure Information

Wednesday, October 24, 2007

12:30 PM - 2:00 PM


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