Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction
| العنوان: | Treatment With Treprostinil and Metformin Normalizes Hyperglycemia and Improves Cardiac Function in Pulmonary Hypertension Associated With Heart Failure With Preserved Ejection Fraction |
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| المؤلفون: | Elena A. Goncharova, Gunner Halliday, Taijyu Satoh, Timothy N. Bachman, Jian Hu, Charles F. McTiernan, Joshua R. Huot, Dmitry A. Goncharov, Yang Bai, Rebecca Vanderpool, Roberto Machado, Longfei Wang, Amanda Fisher, Robert V. Considine, Jeffrey J. Baust, Ana L. Mora, Mark T. Gladwin, Todd G. Cook, Andrea Sebastiani, Jiangning Tan, Yen Chun Lai, T. Avolio, Andrea Bonetto |
| المصدر: | Arterioscler Thromb Vasc Biol Arteriosclerosis, thrombosis, and vascular biology, vol 40, iss 6 |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Leptin, 0301 basic medicine, Male, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, AMP-Activated Protein Kinases, Inbred C57BL, Cardiovascular, Mice, 0302 clinical medicine, Receptors, Lung, Metabolic Syndrome, Diabetes, Heart, Pulmonary, Metformin, Heart Disease, 5.1 Pharmaceuticals, 6.1 Pharmaceuticals, Hypertension, Cardiology, Receptors, Leptin, Left heart disease, Development of treatments and therapeutic interventions, Cardiology and Cardiovascular Medicine, medicine.drug, Cardiac function curve, medicine.medical_specialty, Hypertension, Pulmonary, Clinical Sciences, Diet, High-Fat, metabolic syndrome, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, Animals, Hypoglycemic Agents, Obesity, Metabolic and endocrine, Antihypertensive Agents, Nutrition, Heart Failure, business.industry, treprostinil, Evaluation of treatments and therapeutic interventions, Stroke Volume, medicine.disease, Pulmonary hypertension, Epoprostenol, Diet, Rats, Mice, Inbred C57BL, High-Fat, 030104 developmental biology, glucose intolerance, Cardiovascular System & Hematology, Hyperglycemia, Metabolic syndrome, Insulin Resistance, Heart failure with preserved ejection fraction, business, Treprostinil |
| الوصف: | Objective:Pulmonary hypertension (PH) due to left heart disease (group 2), especially in the setting of heart failure with preserved ejection fraction (HFpEF), is the most common cause of PH worldwide; however, at present, there is no proven effective therapy available for its treatment. PH-HFpEF is associated with insulin resistance and features of metabolic syndrome. The stable prostacyclin analog, treprostinil, is an effective and widely used Food and Drug Administration-approved drug for the treatment of pulmonary arterial hypertension. While the effect of treprostinil on metabolic syndrome is unknown, a recent study suggests that the prostacyclin analog beraprost can improve glucose intolerance and insulin sensitivity. We sought to evaluate the effectiveness of treprostinil in the treatment of metabolic syndrome-associated PH-HFpEF.Approach and Results:Treprostinil treatment was given to mice with mild metabolic syndrome-associated PH-HFpEF induced by high-fat diet and to SU5416/obese ZSF1 rats, a model created by the treatment of rats with a more profound metabolic syndrome due to double leptin receptor defect (obese ZSF1) with a vascular endothelial growth factor receptor blocker SU5416. In high-fat diet-exposed mice, chronic treatment with treprostinil reduced hyperglycemia and pulmonary hypertension. In SU5416/Obese ZSF1 rats, treprostinil improved hyperglycemia with similar efficacy to that of metformin (a first-line drug for type 2 diabetes mellitus); the glucose-lowering effect of treprostinil was further potentiated by the combined treatment with metformin. Early treatment with treprostinil in SU5416/Obese ZSF1 rats lowered pulmonary pressures, and a late treatment with treprostinil together with metformin improved pulmonary artery acceleration time to ejection time ratio and tricuspid annular plane systolic excursion with AMPK (AMP-activated protein kinase) activation in skeletal muscle and the right ventricle.Conclusions:Our data suggest a potential use of treprostinil as an early treatment for mild metabolic syndrome-associated PH-HFpEF and that combined treatment with treprostinil and metformin may improve hyperglycemia and cardiac function in a more severe disease. |
| وصف الملف: | application/pdf |
| تدمد: | 1524-4636 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::15a606dca2088db7c61a4384a37d651fTest https://pubmed.ncbi.nlm.nih.gov/32966132Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....15a606dca2088db7c61a4384a37d651f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 |
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