Divergent cardiopulmonary actions of heme oxygenase enzymatic products in chronic hypoxia
| العنوان: | Divergent cardiopulmonary actions of heme oxygenase enzymatic products in chronic hypoxia |
|---|---|
| المؤلفون: | S. Alex Mitsialis, Xiaoli Liu, Olin D. Liang, Angeles Fernandez-Gonzalez, Helen Christou, Stella Kourembanas, Xinqi Wu, Sally H. Vitali, Francis X. McGowan |
| المصدر: | PLoS ONE, Vol 4, Iss 6, p e5978 (2009) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Vascular smooth muscle, Genotype, Bilirubin, Cardiovascular Disorders, Myocytes, Smooth Muscle, Cardiovascular Disorders/Heart Failure, lcsh:Medicine, Apoptosis, Mice, Transgenic, 030204 cardiovascular system & hematology, Pharmacology, Muscle, Smooth, Vascular, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cell Movement, Fibrosis, medicine, Animals, Myocytes, Cardiac, Hypoxia, lcsh:Science, Cell Proliferation, 030304 developmental biology, Cardiovascular Disorders/Pulmonary Vascular Diseases, 0303 health sciences, Multidisciplinary, Cell Death, lcsh:R, Hypoxia (medical), medicine.disease, Pulmonary hypertension, Rats, 3. Good health, Heme oxygenase, medicine.anatomical_structure, chemistry, Heme Oxygenase (Decyclizing), Immunology, Vascular resistance, Ventricular pressure, cardiovascular system, lcsh:Q, medicine.symptom, Research Article |
| الوصف: | BACKGROUND Hypoxia and pressure-overload induce heme oxygenase-1 (HO-1) in cardiomyocytes and vascular smooth muscle cells (VSMCs). HO-1(-/-) mice exposed to chronic hypoxia develop pulmonary arterial hypertension (PAH) with exaggerated right ventricular (RV) injury consisting of dilation, fibrosis, and mural thrombi. Our objective was to identify the HO-1 product(s) mediating RV protection from hypoxic injury in HO-1(-/-) mice. METHODOLOGY/PRINCIPAL FINDINGS HO-1(-/-) mice were exposed to seven weeks of hypoxia and treated with inhaled CO or biliverdin injections. CO reduced right ventricular systolic pressure (RVSP) and prevented hypoxic pulmonary arteriolar remodeling in both HO-1(-/-) and control mice. Biliverdin had no significant effect on arteriolar remodeling or RVSP in either genotype. Despite this, biliverdin prevented RV failure in the hypoxic HO-1(-/-) mice (0/14 manifested RV wall fibrosis or thrombus), while CO-treated HO-1(-/-) mice developed RV insults similar to untreated controls. In vitro, CO inhibited hypoxic VSMC proliferation and migration but did not prevent cardiomyocyte death from anoxia-reoxygenation (A-R). In contrast, bilirubin limited A-R-induced cardiomyocyte death but did not inhibit VSMC proliferation and migration. CONCLUSIONS/SIGNIFICANCE CO and bilirubin have distinct protective actions in the heart and pulmonary vasculature during chronic hypoxia. Moreover, reducing pulmonary vascular resistance may not prevent RV injury in hypoxia-induced PAH; supporting RV adaptation to hypoxia and preventing RV failure must be a therapeutic goal. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8a5121cbc5f725117ca98f0f929f5dc http://europepmc.org/articles/PMC2694354?pdf=render |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e8a5121cbc5f725117ca98f0f929f5dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
|---|