Presenter Information

Haoyu Zhao, University of Wyoming

Department

Department of Nursin

First Advisor

Dr. Asli Ceylan Isik

Description

In the modern society, obesity has become the major risk factor of heart diseases. Endothelin - 1 (ET - 1), which plays an important role in regulating cardiovascular functions, mediates its effects on cardiovascular system through its receptors, endothelin receptor - 1A (ET A ), that are abundant in the heart. To investigate the role of ET A on obesity - induced cardiac dysfunction, we randomly assi gned Endothelin - 1 receptor A knockout (ETAKO) mice and wild - type C57BL/6 mice to receive either high - (45% fat) (HF) or low - (10% fat) (LF) fat diets starting from their 5 - 6 weeks of age for 24 weeks. HF - diet enhanced body weight, heart weight and size, an d impaired glucose tolerance in C57BL/6. Although ETAKO did not have altered glucose tolerance, it was associated with a reduction in body weight, heart weight and size. Echocardiography revealed that increased left ventricular mass and wall thickness in C 57BL/6 HF - fed mice, which were mitigated by ETAKO. HF - diet compromised myocardial contractile f unction and intracellular Ca 2+ handling, which were significantly attenuated by ETAKO. Western blot demonstrated that HF - diet increased the levels of hypertrophy - related proteins and reduced the levels of autophagy - related proteins whereas contrasting results were seen with EKTO - ETAKO reduced the hypertrophy - related protein expressions while increasing autophagy - related protein expressions. Our results suggest ETA KO may rescue the heart from obesity - associated cardiac dysfunction . Key Words: endothelin receptor A, high fat diet, cardiac hypertrophy

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Oral and Poster Presentation, Wyoming NSF EPSCoR

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Targeting Endothelin Receptor - 1A (ET A ) to Prevent Obesity - Induced Cardiac Dysfunction

In the modern society, obesity has become the major risk factor of heart diseases. Endothelin - 1 (ET - 1), which plays an important role in regulating cardiovascular functions, mediates its effects on cardiovascular system through its receptors, endothelin receptor - 1A (ET A ), that are abundant in the heart. To investigate the role of ET A on obesity - induced cardiac dysfunction, we randomly assi gned Endothelin - 1 receptor A knockout (ETAKO) mice and wild - type C57BL/6 mice to receive either high - (45% fat) (HF) or low - (10% fat) (LF) fat diets starting from their 5 - 6 weeks of age for 24 weeks. HF - diet enhanced body weight, heart weight and size, an d impaired glucose tolerance in C57BL/6. Although ETAKO did not have altered glucose tolerance, it was associated with a reduction in body weight, heart weight and size. Echocardiography revealed that increased left ventricular mass and wall thickness in C 57BL/6 HF - fed mice, which were mitigated by ETAKO. HF - diet compromised myocardial contractile f unction and intracellular Ca 2+ handling, which were significantly attenuated by ETAKO. Western blot demonstrated that HF - diet increased the levels of hypertrophy - related proteins and reduced the levels of autophagy - related proteins whereas contrasting results were seen with EKTO - ETAKO reduced the hypertrophy - related protein expressions while increasing autophagy - related protein expressions. Our results suggest ETA KO may rescue the heart from obesity - associated cardiac dysfunction . Key Words: endothelin receptor A, high fat diet, cardiac hypertrophy