UVM Theses and Dissertations
Format:
Print
Author:
Yi, Ting
Dept./Program:
Molecular Physiology and Biophysics
Year:
2013
Degree:
Ph. D.
Abstract:
Heart failure remains the leading cause of mobidity and mortality worldwide. Cardiac systolic and diastolic dysfunction are the main contributors to the development of heart failure. Patients with diabetes have also been shown to exhibit cardiac irregularity, and this is often correlated with poor relaxation function. These diabetic patients usually develop diabetic cardiomyopathy. Chronic exposure to oxidative stress has been demonstrated to accompany diabetes and it is an important factor in causing abnormal calcium handling. Therefore, elucidating mechanisms underlying cardiac dysfunction, especially with the background of diabetes and oxidative stress, is clearly warranted.
Cardiac zinc content has been shown to correlate positively with ejection fraction in human hearts. Zinc as a supplementation partially preserved the loss of cardiac function due to ischemia/reperfusion injury, diabetes, hypertension, etc. One common phenomenon behind these diseases is the accumulation of high oxidative stress level. Zinc is an antioxidant metal, protecting the function of sulfhydryl groups in cysteine residues. It is reasonable to expect that the role of zinc in improving cardiac performance is partially mediated through the redox signaling pathway.
In chapter 2, we examined the effects of zinc on cardiac function in general. Zinc reduces systolic and diastolic calcium, and increases diastolic sarcomere length, which is achieved by partially blocking L-type channels and decreasing ryanodine receptor phosphorylation. The two effects combined significantly lower the high calcium content in diabetes and restore sarcomere contraction to normal, as shown in chapter 3. These data suggest that zinc could be potentially used to treat diabetic patients with associated cardiac diastolic dysfunction. Since oxidative stress is prevalent in diabetes, we examined the effects of hydrogen peroxide-induced oxidation levels in cardiomyocyte, myofibril and myosin levels in chapter 4.
Cardiac zinc content has been shown to correlate positively with ejection fraction in human hearts. Zinc as a supplementation partially preserved the loss of cardiac function due to ischemia/reperfusion injury, diabetes, hypertension, etc. One common phenomenon behind these diseases is the accumulation of high oxidative stress level. Zinc is an antioxidant metal, protecting the function of sulfhydryl groups in cysteine residues. It is reasonable to expect that the role of zinc in improving cardiac performance is partially mediated through the redox signaling pathway.
In chapter 2, we examined the effects of zinc on cardiac function in general. Zinc reduces systolic and diastolic calcium, and increases diastolic sarcomere length, which is achieved by partially blocking L-type channels and decreasing ryanodine receptor phosphorylation. The two effects combined significantly lower the high calcium content in diabetes and restore sarcomere contraction to normal, as shown in chapter 3. These data suggest that zinc could be potentially used to treat diabetic patients with associated cardiac diastolic dysfunction. Since oxidative stress is prevalent in diabetes, we examined the effects of hydrogen peroxide-induced oxidation levels in cardiomyocyte, myofibril and myosin levels in chapter 4.