The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function
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Case Western Reserve University School of Graduate Studies / OhioLINK
2011
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| Online Access: | http://rave.ohiolink.edu/etdc/view?acc_num=case1296007529 |
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ndltd-OhioLink-oai-etd.ohiolink.edu-case12960075292021-08-03T05:33:51Z The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function Christopher, Bridgette A. Physiology TnI myocardial infarction high saturated fat myocardial insulin resistance <p>In the first study, a rat model of low myocardial blood flow tested whether post-translational changes to proteins of the thin and thick muscle filaments correlate with decreased cardiac contractility. Following three days of low blood flow, cardiac trabeculae demonstrated a reduction in fractional shortening at rest and a relative decline in fractional shortening when challenged with high dose dobutamine, reflecting reduced energy reserves. Permeabilized fibers from low blood flow hearts demonstrated a decline in maximum force and Ca2+ sensitivity. An examination of sarcomeric proteins by two-dimensional gel electrophoresis, mass spectrometry, and phospho-specific antibodies showed Ser23/24 and Ser43/45 phosphorylation of troponin I (TnI). Total TnI phosphorylation was not different between the groups, but Ser23/24 phosphorylation declined with low blood flow, implying an accompanying increase in Ser43/45 phosphorylation of TnI. These findings suggest that altered TnI function, due to changes in the distribution of phosphorylated sites, is an early contributor to reduced contractility of the heart.</p><p>Previous studies have reported that high fat feeding in mild to moderate heart failure (HF) results in the preservation of contractile function, suggesting that preventing the switch from fatty acid to glucose metabolism in HF may ameliorate dysfunction. Insulin resistance is one potential mechanism for regulating substrate utilization, and the second study sought to determine whether peripheral and myocardial insulin resistance exists with HF and/or high fat diet. Rats underwent coronary artery ligation (HF) or sham surgery and were randomized to normal chow (NC) or high fat diet (SAT) for eight weeks. HF+SAT showed preserved systolic and diastolic function compared to HF+NC. Glucose tolerance tests revealed peripheral insulin resistance in SHAM+SAT, HF+NC, and HF+SAT compared to SHAM+NC. Positron emission tomography imaging confirmed myocardial insulin resistance only in HF+SAT. Western blot analysis of insulin signaling protein expression was indicative of cardiac insulin resistance in HF+SAT. In conclusion, HF animals fed high saturated fat exhibit preserved myocardial contractile function, peripheral and myocardial insulin resistance, decreased myocardial glucose utilization rate and alterations in cardiac insulin signaling. These results suggest that myocardial insulin resistance may serve a cardioprotective function with high fat feeding in mild to moderate heart failure.</p> 2011 English text Case Western Reserve University School of Graduate Studies / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=case1296007529 http://rave.ohiolink.edu/etdc/view?acc_num=case1296007529 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws. |
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NDLTD |
| language |
English |
| sources |
NDLTD |
| topic |
Physiology TnI myocardial infarction high saturated fat myocardial insulin resistance |
| spellingShingle |
Physiology TnI myocardial infarction high saturated fat myocardial insulin resistance Christopher, Bridgette A. The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| author |
Christopher, Bridgette A. |
| author_facet |
Christopher, Bridgette A. |
| author_sort |
Christopher, Bridgette A. |
| title |
The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| title_short |
The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| title_full |
The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| title_fullStr |
The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| title_full_unstemmed |
The Influence of Myofilament Protein Modification and Myocardial Insulin Resistance on Pathologic Left Ventricular Function |
| title_sort |
influence of myofilament protein modification and myocardial insulin resistance on pathologic left ventricular function |
| publisher |
Case Western Reserve University School of Graduate Studies / OhioLINK |
| publishDate |
2011 |
| url |
http://rave.ohiolink.edu/etdc/view?acc_num=case1296007529 |
| work_keys_str_mv |
AT christopherbridgettea theinfluenceofmyofilamentproteinmodificationandmyocardialinsulinresistanceonpathologicleftventricularfunction AT christopherbridgettea influenceofmyofilamentproteinmodificationandmyocardialinsulinresistanceonpathologicleftventricularfunction |
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