Apolipoprotein A-I mimetic peptide 4F rescues pulmonary hypertension by inducing microRNA-193-3p
| Autor: | François Potus, David Meriwether, Soban Umar, Mohamad Navab, Andrea Iorga, Sébastien Bonnet, Gabriel Wong, Srinivasa T. Reddy, Kaveh Navab, Mansoureh Eghbali, Alan M. Fogelman, Salil Sharma, Steeve Provencher, Sandra Breuils-Bonnet, David J. Ross, Denise Mai |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Apolipoprotein B Cardiorespiratory Medicine and Haematology Inbred C57BL Cardiovascular Muscle Smooth Vascular Receptor IGF Type 1 Rats Sprague-Dawley Mice pulmonary arterial hypertension Hydroxyeicosatetraenoic Acids Medicine Lung Cells Cultured apolipoprotein A-I mimetic peptide 4F Cultured biology Hydroxyeicosatetraenoic acid Pulmonary microRNAs medicine.anatomical_structure Hypertension Public Health and Health Services Muscle Smooth medicine.symptom Cardiology and Cardiovascular Medicine Receptor Biotechnology medicine.medical_specialty Hypertension Pulmonary Cells Clinical Sciences Article Rare Diseases Physiology (medical) Internal medicine Vascular miR-193 microRNA Animals Humans IGF Type 1 human Cell Proliferation Retinoid X Receptor alpha business.industry Vascular disease Cell growth Hypoxia (medical) medicine.disease Pulmonary hypertension Rats Mice Inbred C57BL lipoproteins MicroRNAs Endocrinology Cardiovascular System & Hematology biology.protein Sprague-Dawley business Peptides |
| Zdroj: | Circulation, vol 130, iss 9 |
| Popis: | Background— Pulmonary arterial hypertension is a chronic lung disease associated with severe pulmonary vascular changes. A pathogenic role of oxidized lipids such as hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids is well established in vascular disease. Apolipoprotein A-I mimetic peptides, including 4F, have been reported to reduce levels of these oxidized lipids and improve vascular disease. However, the role of oxidized lipids in the progression of pulmonary arterial hypertension and the therapeutic action of 4F in pulmonary arterial hypertension are not well established. Methods and Results— We studied 2 different rodent models of pulmonary hypertension (PH): a monocrotaline rat model and a hypoxia mouse model. Plasma levels of hydroxyeicosatetraenoic and hydroxyoctadecadienoic acids were significantly elevated in PH. 4F treatment reduced these levels and rescued preexisting PH in both models. MicroRNA analysis revealed that microRNA-193-3p (miR193) was significantly downregulated in the lung tissue and serum from both patients with pulmonary arterial hypertension and rodents with PH. In vivo miR193 overexpression in the lungs rescued preexisting PH and resulted in downregulation of lipoxygenases and insulin-like growth factor-1 receptor. 4F restored PH-induced miR193 expression via transcription factor retinoid X receptor α. Conclusions— These studies establish the importance of microRNAs as downstream effectors of an apolipoprotein A-I mimetic peptide in the rescue of PH and suggest that treatment with apolipoprotein A-I mimetic peptides or miR193 may have therapeutic value. |
| Databáze: | OpenAIRE |
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