Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism
| العنوان: | Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism |
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| المؤلفون: | Jeanette N. McClintick, Adam G. Goodwill, Kieren J. Mather, B. Paul Herring, Johnathan D. Tune, Abass M. Conteh, Jillian N. Noblet, Daniel J. Sassoon |
| المصدر: | Basic Research in Cardiology. 111 |
| بيانات النشر: | Springer Science and Business Media LLC, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Proteomics, 0301 basic medicine, Cardiac function curve, medicine.medical_specialty, Swine, Physiology, Ischemia, Myocardial Reperfusion Injury, 030204 cardiovascular system & hematology, Glucagon, Article, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, 0302 clinical medicine, Glucagon-Like Peptide 1, Physiology (medical), Internal medicine, medicine, Hyperinsulinemia, Animals, Obesity, Oligonucleotide Array Sequence Analysis, biology, business.industry, Gene Expression Profiling, Stroke volume, medicine.disease, Troponin, Disease Models, Animal, 030104 developmental biology, Blood pressure, Endocrinology, Coronary occlusion, biology.protein, Transcriptome, Cardiology and Cardiovascular Medicine, business |
| الوصف: | This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miRNA) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-minutes coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect the blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca(2+) binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion. |
| تدمد: | 1435-1803 0300-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c7465a0f9a0192cc772a9e56f0b4415Test https://doi.org/10.1007/s00395-016-0563-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1c7465a0f9a0192cc772a9e56f0b4415 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14351803 03008428 |
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