divergent cardiopulmonary actions of heme oxygenase enzymatic products in chronic hypoxia发散心肺的行为在慢性低氧血红素加氧酶酶产品.pdfVIP

Divergent Cardiopulmonary Actions of Heme Oxygenase Enzymatic Products in Chronic Hypoxia 1 2 2 3 2 Sally H. Vitali , S. Alex Mitsialis , Olin D. Liang , Xiaoli Liu , Angeles Fernandez-Gonzalez , Helen 4 4 5 2 Christou , Xinqi Wu , Francis X. McGowan , Stella Kourembanas * 1 Division of Critical Care Medicine, Children’s Hospital Boston, Boston, Massachusetts, United States of America, 2 Division of Newborn Medicine, Children’s Hospital Boston, Boston, Massachusetts, United States of America, 3 Pulmonary Division, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America, 4 Division of Newborn Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, United States of America, 5 Division of Cardiac Anesthesia, Children’s Hospital Boston, Boston, Massachusetts, United States of America Abstract Background: Hypoxia and pressure-overload induce heme oxygenase-1 (HO-1) in cardiomyocytes and vascular smooth muscle cells (VSMCs). HO-12/ 2 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 indentify the HO-1 product(s) mediating RV protection from hypoxic injury in HO-12/ 2 mice. Methodology/Principal Findings: HO-12/ 2 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-12/ 2 and control mice. Biliverdin had no significant effect on arteriolar remodeling or RVSP in either geno