Abstract 18863: Emerging Role of Cytoglobin in Cardiovascular Function and Regulation: Evidence From Cytoglobin Knockout Mice
Cytoglobin (Cygb), a recently identified globin protein, is reported to play an important role in O2-dependent nitric oxide (NO) removal, nitrite reduction and NO production; and it is thought to be involved in vascular function. However, there is no report on the effect of Cygb in cardiovascular (CV) function. Recently, a genetically modified mouse model with global absence of Cygb was developed. Therefore, to investigate the role of Cygb in CV function and regulation, we utilized this mouse model to explore the role of Cygb for in vivo (echocardiography) and in vitro (isolated perfused hearts) cardiac hemodynamics. Tail-cuff BP measured in conscious animals was >20 mmHg lower in Cygb-knockout (Cygb-KO) mice than in age-matched (6-months) wild-type (WT) mice. Importantly, echocardiographic parameters in Cygb-KO mice were markedly different from WT mice (Table). Cardiac chambers in Cygb-KO mice were significantly larger with increased end-systolic and end-diastolic volumes; however, there was septal hypertrophy with large stroke volume, but no differences in heart rate or fractional shortening. In isolated hearts, coronary flow was significantly higher in Cygb-KO hearts, but other parameters were comparable (Table). Thus, the absence of Cygb results in marked hypotension, ventricular chamber dilatation and dysfunction yet with preserved cardiac contractile function. Collectively, these data from both in vivo and in vitro studies provide direct evidence that Cygb plays a critical role in CV pathophysiology, and its absence during stressful conditions may lead to progressive high output cardiomyopathy or heart failure that warrants in-depth investigation.
- © 2013 by American Heart Association, Inc.