Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing

التفاصيل البيبلوغرافية
العنوان: Protection against pressure overload-induced right heart failure by uncoupling protein 2 silencing
المؤلفون: Oleg Pak, Rolf Schreckenberg, Daniela Haag, Annemarie Wolf, Ralph T. Schermuly, Christine Hirschhäuser, Natascha Sommer, Susanne Rohrbach, Matthias Hecker, Rainer Schulz, Martin Weber, Ludger Fink, N. Weißmann, Baktybek Kojonazarov, Ling Li, Azadeh Esfandiary, Werner Seeger, Akylbek Sydykov, Hossein Ardeschir Ghofrani, Hanna Sarah Kutsche, Klaus-Dieter Schlüter
المصدر: Cardiovascular Research
بيانات النشر: Oxford University Press (OUP), 2019.
سنة النشر: 2019
مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Cardiac output, Physiology, Hypertension, Pulmonary, Spotlight Original Articles, 030204 cardiovascular system & hematology, Collagen Type I, Mitochondria, Heart, Ventricular Function, Left, Pulmonary hypertension, Muscle hypertrophy, Pulmonary artery banding, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Physiology (medical), Internal medicine, Cardiac remodelling, medicine, Animals, Myocyte, Myocytes, Cardiac, Uncoupling Protein 2, Gene Silencing, Cells, Cultured, Heart Failure, Mice, Knockout, Pressure overload, Hypertrophy, Right Ventricular, Ventricular Remodeling, business.industry, Fibroblasts, medicine.disease, Cardiac protection, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Ventricular Function, Right, Ventricular pressure, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, business
الوصف: Aims The role of uncoupling protein 2 (UCP2) in cardiac adaptation to pressure overload remains unclear. In a classical model of left ventricular pressure overload genetic deletion of UCP2 (UCP2−/−) protected against cardiac hypertrophy and failure. However, in UCP2−/− mice increased proliferation of pulmonary arterial smooth muscle cells induces mild pulmonary hypertension, right ventricular (RV) hypertrophy, and reduced cardiac output. This suggests a different role for UCP2 in RV and left ventricular adaptation to pressure overload. To clarify this situation in more detail UCP2−/− and wild-type mice were exposed to pulmonary arterial banding (PAB). Methods and results Mice were analysed (haemodynamics, morphometry, and echocardiography) 3 weeks after PAB or sham surgery. Myocytes and non-myocytes were isolated and analysed separately. Cell shortening of myocytes and fura-2 loading of cardiomyocytes were used to characterize their function. Brd assay was performed to study fibroblast proliferation. Isolated mitochondria were analysed to investigate the role of UCP2 for reactive oxygen species (ROS) production. UCP2 mRNA was 2.7-fold stronger expressed in RV myocytes than in left ventricular myocytes and stronger expressed in non-myocytes compared with myocytes. Three weeks after PAB, cardiac output was reduced in wild type but preserved in UCP2−/− mice. UCP2−/− had increased RV wall thickness, but lower RV internal diameters and displayed a significant stronger fibrosis. Cardiac fibroblasts from UCP2−/− had reduced proliferation rates but higher collagen-1 expression. Myocytes isolated from mice after PAB banding showed preserved function that was further improved by UCP2−/−. Mitochondrial ROS production and respiration was similar between UCP2−/− or wild-type hearts. Conclusion Despite a mild pulmonary hypertension in UCP2−/− mice, hearts from these mice are well preserved against additional pressure overload (severe pulmonary hypertension). This—at least in part—depends on different behaviour of non-myocytes (fibroblasts).
تدمد: 1755-3245
0008-6363
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a1b5464515684045eeb647bdd62cb422Test
https://doi.org/10.1093/cvr/cvz049Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....a1b5464515684045eeb647bdd62cb422
قاعدة البيانات: OpenAIRE