Project Title

The Role of the Ataxia Telangiectasia Mutated Kinase on Diastolic and Systolic Function in Diabetic Cardiomyopathy

Authors' Affiliations

Pearl McCuistion, Department of Biological Sciences, College of Arts and Sciences, The Ronald McNair Post Baccalaureate Program, East Tennessee State University, Johnson City, TN. Cerrone R. Foster, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN. Laura Daniel, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN. Krishna Singh, Department of Biological Sciences, College of Arts and Sciences, East Tennessee State University, Johnson City, TN.

Location

White Top Mtn

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

117

Faculty Sponsor’s Department

Biological Sciences

Name of Project's Faculty Sponsor

Dr. Cerrone Foster

Type

Poster: Competitive

Classification of First Author

Undergraduate Student

Project's Category

Biological Sciences, Cardiovascular System, Cardiovascular Disease, Diabetes

Abstract Text

In a replicating cell, the ataxia telangiectasia mutated kinase (ATM) gene induces DNA repair or cell cycle arrest in response to DNA damage. Mutations in the ATM gene have been shown to predispose individuals to insulin resistance and cardiovascular disease (CVD). CVD is a leading cause of death in the United States and diabetes has recently been identified as an increased risk factor for CVD. Diastolic dysfunction is an early indicator of CVD in diabetics. This can be caused by cardiac fibrosis or hypertrophic cardiomyopathy. Studies have also shown that females with diabetes are at an increased risk for CVD when compared to diabetic males. Therefore, the effects of ATM deficiency on diabetic heart function in both male and female mice were studied. Mice with two normal copies (WT) and one mutate copy (hKO) for the ATM gene were treated with 150 mg/kg body weight dose of streptozotocin (STZ) at ten months of age to induce diabetes. Three days following, blood glucose levels were measured. Mice with blood glucose levels above 300 mg/dL were considered diabetic and used for the study. The animals were followed over a time period of two months. Echocardiography was used to examine cardiac function. Blood flow velocity and ventricular filling parameters were measured in ATM WT and hKO diabetic mice. Contraction and relaxation times of the left ventricle were also measured in these mice. The animals were euthanized at two months post-treatment. Echocardiography revealed that ATM deficiency resulted in a greater increase in systolic function in hKO diabetic females compared to non-diabetic females with the same genotype. Systolic function in WT-diabetic female mice was not higher in non-diabetic females however it was higher compared to WT diabetic males. Interestingly, WT-diabetic female mice also experienced a higher systolic function compared to hKO-diabetic females. Doppler blood flow velocity patterns will be analyzed to determine ATM effects on diastolic dysfunction. These findings should help to better understand the physiological changes the ATM gene has in diabetic cardiomyopathy. It should also help identify if ATM deficiency is a risk factor for diabetics who also suffer from cardiovascular disease.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

The Role of the Ataxia Telangiectasia Mutated Kinase on Diastolic and Systolic Function in Diabetic Cardiomyopathy

White Top Mtn

In a replicating cell, the ataxia telangiectasia mutated kinase (ATM) gene induces DNA repair or cell cycle arrest in response to DNA damage. Mutations in the ATM gene have been shown to predispose individuals to insulin resistance and cardiovascular disease (CVD). CVD is a leading cause of death in the United States and diabetes has recently been identified as an increased risk factor for CVD. Diastolic dysfunction is an early indicator of CVD in diabetics. This can be caused by cardiac fibrosis or hypertrophic cardiomyopathy. Studies have also shown that females with diabetes are at an increased risk for CVD when compared to diabetic males. Therefore, the effects of ATM deficiency on diabetic heart function in both male and female mice were studied. Mice with two normal copies (WT) and one mutate copy (hKO) for the ATM gene were treated with 150 mg/kg body weight dose of streptozotocin (STZ) at ten months of age to induce diabetes. Three days following, blood glucose levels were measured. Mice with blood glucose levels above 300 mg/dL were considered diabetic and used for the study. The animals were followed over a time period of two months. Echocardiography was used to examine cardiac function. Blood flow velocity and ventricular filling parameters were measured in ATM WT and hKO diabetic mice. Contraction and relaxation times of the left ventricle were also measured in these mice. The animals were euthanized at two months post-treatment. Echocardiography revealed that ATM deficiency resulted in a greater increase in systolic function in hKO diabetic females compared to non-diabetic females with the same genotype. Systolic function in WT-diabetic female mice was not higher in non-diabetic females however it was higher compared to WT diabetic males. Interestingly, WT-diabetic female mice also experienced a higher systolic function compared to hKO-diabetic females. Doppler blood flow velocity patterns will be analyzed to determine ATM effects on diastolic dysfunction. These findings should help to better understand the physiological changes the ATM gene has in diabetic cardiomyopathy. It should also help identify if ATM deficiency is a risk factor for diabetics who also suffer from cardiovascular disease.