| First Author | Mammen PP | Year | 2003 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 285 |
| Issue | 5 | Pages | H2132-41 |
| PubMed ID | 12881221 | Mgi Jnum | J:86546 |
| Mgi Id | MGI:2680745 | Doi | 10.1152/ajpheart.00147.2003 |
| Citation | Mammen PP, et al. (2003) Hypoxia-induced left ventricular dysfunction in myoglobin-deficient mice. Am J Physiol Heart Circ Physiol 285(5):H2132-41 |
| abstractText | Myoglobin-deficient mice are viable and have preserved cardiac function due to their ability to mount a complex compensatory response involving increased vascularization and the induction of the hypoxia gene program (hypoxia-inducible factor-1alpha, endothelial PAS, heat shock protein27, etc.). To further define and explore functional roles for myoglobin, we challenged age- and gender-matched wild-type and myoglobin-null mice to chronic hypoxia (10% oxygen for 1 day to 3 wk). We observed a 30% reduction in cardiac systolic function in the myoglobin mutant mice exposed to chronic hypoxia with no changes observed in the wild-type control hearts. The cardiac dysfunction observed in the hypoxic myoglobin-null mice was reversible with reexposure to normoxic conditions and could be prevented with treatment of an inhibitor of nitric oxide (NO) synthases. These results support the conclusion that hypoxia-induced cardiac dysfunction in myoglobin-null mice occurs via a NO-mediated mechanism. Utilizing enzymatic assays for NO synthases and immunohistochemical analyses, we observed a marked induction of inducible NO synthase in the hypoxic myoglobin mutant ventricle compared with the wild-type hypoxic control ventricle. These new data establish that myoglobin is an important cytoplasmic cardiac hemoprotein that functions in regulating NO homeostasis within cardiomyocytes. |
