The p66ShcA adaptor protein regulates healing after myocardial infarction
| العنوان: | The p66ShcA adaptor protein regulates healing after myocardial infarction |
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| المؤلفون: | Andrea Carpi, Dusan Bilbija, Tania Zaglia, Julia Sagave, Marika Campesan, Jarle Vaage, Lars Gullestad, Marco Giorgio, Fabio Di Lisa, Marco Mongillo, Anton Baysa, Maria Troitskaya, Guro Valen, Christen P. Dahl |
| المصدر: | Basic Research in Cardiology. 110 |
| بيانات النشر: | Springer Science and Business Media LLC, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Male, Physiology, Cardiac fibrosis, Myocardial Infarction, Fluorescent Antibody Technique, Matrix metalloproteinase, Inbred C57BL, medicine.disease_cause, Mice, Collagen, Healing, Heart rupture, MMP-2, Myocardial infarction, ShcA, Aged, Animals, Blotting, Western, Female, Humans, Immunohistochemistry, Matrix Metalloproteinase 2, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Oxidative Stress, Real-Time Polymerase Chain Reaction, Shc Signaling Adaptor Proteins, Ventricular Remodeling, Cardiology and Cardiovascular Medicine, Physiology (medical), Medicine (all), Blotting, medicine.anatomical_structure, Knockout mouse, cardiovascular system, Cardiology, Western, medicine.medical_specialty, Src Homology 2 Domain-Containing, Transforming Protein 1, Knockout, Heart Rupture, Internal medicine, medicine, cardiovascular diseases, Fibroblast, business.industry, medicine.disease, Heart failure, business, Oxidative stress |
| الوصف: | Heart rupture and heart failure are deleterious complications of myocardial infarction. The ShcA gene encodes for three protein isoforms, p46-, p52- and p66ShcA. p66ShcA induces oxidative stress. We studied the role of p66ShcA post-infarction. Expression of p66ShcA was analyzed in myocardium of patients with stable angina (n = 11), in explanted hearts with end-stage ischemic heart failure (n = 9) and compared to non-failing hearts not suitable for donation (n = 7). p66ShcA was increased in the patients with stable angina, but not in the patients with end-stage heart failure. Mice (n = 105) were subjected to coronary artery ligation. p66ShcA expression and phosphorylation were evaluated over a 6-week period. p66ShcA expression increased transiently during the first weeks post-infarction. p66ShcA knockout mice (KO) were compared to wild type (n = 82 in total). KO had improved survival and reduced occurrence of heart rupture post-infarction. Expression of cardiac matrix metalloproteinase 2 (MMP-2) was reduced; fibroblast activation and collagen accumulation were facilitated, while oxidative stress was attenuated in KO early post-infarction. 6 weeks post-infarction, reactive fibrosis and left ventricular dilatation were diminished in KO. p66ShcA regulation of MMP-2 was demonstrated in cultured fibroblasts: lack or overexpression of p66ShcA in vitro altered expression of MMP-2. Myocardial infarction induced cardiac p66ShcA. Deletion of p66ShcA improved early survival, myocardial healing and reduced cardiac fibrosis. Upon myocardial infarction p66ShcA regulates MMP-2 activation. The role of p66ShcA in human cardiac disease deserves further study as a potential target for reducing adverse cardiac remodeling post-infarction. |
| تدمد: | 1435-1803 0300-8428 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d32e2f410fbba5d252eefa47eff6f9d7Test https://doi.org/10.1007/s00395-015-0470-0Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d32e2f410fbba5d252eefa47eff6f9d7 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14351803 03008428 |
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