Chronic hypoxia induces right heart failure in caveolin-1−/− mice
| العنوان: | Chronic hypoxia induces right heart failure in caveolin-1−/− mice |
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| المؤلفون: | Andres I. Rodriguez, Philip M. Bauer, Yinna Wang, Hunter C. Champion, J. Agustin Cruz, Archana Gangopadhyay, Eileen M. Bauer, Nabil S. Zeineh, Sruti Shiva |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 302:H2518-H2527 |
| بيانات النشر: | American Physiological Society, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | medicine.medical_specialty, Cardiac output, Nitric Oxide Synthase Type III, Physiology, Hypertension, Pulmonary, Caveolin 1, Blood Pressure, Biology, Muscle hypertrophy, Mice, Physiology (medical), Internal medicine, Cyclic GMP-Dependent Protein Kinases, medicine, Animals, Cardiac Output, Hypoxia, Lung, Heart Failure, Mice, Knockout, Hypertrophy, Right Ventricular, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Oxidative Stress, Endocrinology, medicine.anatomical_structure, Blood pressure, Heart failure, cardiovascular system, Cardiology, Signaling and Stress Response, medicine.symptom, Cardiology and Cardiovascular Medicine |
| الوصف: | Caveolin-1 (Cav-1)−/− mice develop mild pulmonary hypertension as they age. In this study, we sought to determine the effect of chronic hypoxia, an established model of pulmonary hypertension, on young Cav-1−/− mice with no measurable signs of pulmonary hypertension. Exposure of Cav-1−/− mice to chronic hypoxia resulted in an initial rise in right ventricular (RV) systolic pressure (RVSP) similar to wild-type (WT) mice. By three weeks RVSP decreased in the Cav-1−/− mice, whereas it was maintained in WT mice. The drop in RVSP in Cav-1−/− mice was accompanied by decreased cardiac output, increased RV hypertrophy, RV interstitial fibrosis, decreased RV sarco(endo)plasmic reticulum Ca2+-ATPase 2a mRNA and decreased RV function compared with WT mice. Importantly, minimal differences were noted in pulmonary vascular remodeling between WT and Cav-1−/− mice, and left ventricular function was normal in hypoxic Cav-1−/− mice. Mechanistically, increased endothelial nitric oxide synthase uncoupling and increased tyrosine nitration of protein kinase G were detected in the RV of Cav-1−/− mice. These hemodynamic, histological, and molecular changes were prevented in Cav-1−/− mice expressing an endothelial-specific Cav-1 transgene or by nitric oxide synthase inhibition. These data suggest that, in Cav-1−/− mice, increased oxidative/nitrosative stress due to endothelial nitric oxide synthase uncoupling modifies the response of the RV to pressure overload, accelerating the deterioration of RV function. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::260c6eed9608dbfc9473d373153e63a8Test https://doi.org/10.1152/ajpheart.01140.2011Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....260c6eed9608dbfc9473d373153e63a8 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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