Alterations in ACE and ACE2 Activities and Cardiomyocyte Signaling Underlie Improved Myocardial Function in a Rat Model of Repeated Remote Ischemic Conditioning
| العنوان: | Alterations in ACE and ACE2 Activities and Cardiomyocyte Signaling Underlie Improved Myocardial Function in a Rat Model of Repeated Remote Ischemic Conditioning |
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| المؤلفون: | Bódi, Beáta, Pilz, Patrick M., Mártha, Lilla, Lang, Miriam, Hamza, Ouafa, Fagyas, Miklós, Szabó, Petra L., Abraham, Dietmar, Tóth, Attila, Podesser, Bruno K., Kiss, Attila, Papp, Zoltán |
| المصدر: | International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 22, Iss 11064, p 11064 (2021) Volume 22 Issue 20 |
| بيانات النشر: | MDPI, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, QH301-705.5, Heart Ventricles, Myocardial Infarction, Carboxypeptidases, Article, Ventricular Function, Left, Rats, Sprague-Dawley, Animals, Myocytes, Cardiac, cardiovascular diseases, Biology (General), Phosphorylation, Ischemic Postconditioning, QD1-999, repeated remote ischemic conditioning, Ventricular Remodeling, cardiomyocyte mechanics, Troponin I, Rats, Chemistry, Disease Models, Animal, cardiovascular system, Angiotensin-Converting Enzyme 2, signaling, Carrier Proteins |
| الوصف: | Post-ischemic left ventricular (LV) remodeling and its hypothetical prevention by repeated remote ischemic conditioning (rRIC) in male Sprague–Dawley rats were studied. Myocardial infarction (MI) was evoked by permanent ligation of the left anterior descending coronary artery (LAD), and myocardial characteristics were tested in the infarcted anterior and non-infarcted inferior LV regions four and/or six weeks later. rRIC was induced by three cycles of five-minute-long unilateral hind limb ischemia and five minutes of reperfusion on a daily basis for a period of two weeks starting four weeks after LAD occlusion. Sham operated animals served as controls. Echocardiographic examinations and invasive hemodynamic measurements revealed distinct changes in LV systolic function between four and six weeks after MI induction in the absence of rRIC (i.e., LV ejection fraction (LVEF) decreased from 52.8 ± 2.1% to 50 ± 1.6%, mean ± SEM, p < 0.05) and in the presence of rRIC (i.e., LVEF increased from 48.2 ± 4.8% to 55.2 ± 4.1%, p < 0.05). Angiotensin-converting enzyme (ACE) activity was about five times higher in the anterior LV wall at six weeks than that in sham animals. Angiotensin-converting enzyme 2 (ACE2) activity roughly doubled in post-ischemic LVs. These increases in ACE and ACE2 activities were effectively mitigated by rRIC. Ca2+-sensitivities of force production (pCa50) of LV permeabilized cardiomyocytes were increased at six weeks after MI induction together with hypophosphorylation of 1) cardiac troponin I (cTnI) in both LV regions, and 2) cardiac myosin-binding protein C (cMyBP-C) in the anterior wall. rRIC normalized pCa50, cTnI and cMyBP-C phosphorylations. Taken together, post-ischemic LV remodeling involves region-specific alterations in ACE and ACE2 activities together with changes in cardiomyocyte myofilament protein phosphorylation and function. rRIC has the potential to prevent these alterations and to improve LV performance following MI. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::316b7ec4c174919271b439fd9e9f00dfTest http://europepmc.org/articles/PMC8537248Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....316b7ec4c174919271b439fd9e9f00df |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14220067 |
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