Bmx non‐receptor tyrosine kinase mediation of hypoxic signaling in the adult myocardium

Abstract

Myocardial ischemia, a reduction in arterial blood flow to the heart muscle, often results in cell death and is critically mediated by both the angiogenic capacity of the myocardium and the ability of the target tissue itself to resist injury. Recent evidence has suggested a novel role for the non-receptor tyrosine kinase Bmx in growth factor dependent angiogenesis and response to ischemia. However, the role of this protein in myocardial injury is unknown. In the present study, we used CD31 and lectin staining of endothelial cells in the adult mouse to reveal capillary density in the normal and ischemic heart. To evaluate the role of Bmx in the myocardium, immunoblotting of whole heart lysates as well as of isolated myocytes was used to detect protein expression in the adult animal. Likewise, confocal imaging was used to detect the presence of Bmx within the anatomical context of the heart and to localize it with specific associating proteins. In the isolated myocyte setting, the effects of hypoxia/reoxygenation on mRNA expression, total protein expression and phosphorylation of Bmx and its associated family members was examined along with an evaluation of the involvement of potential regulatory proteins. Coupled with studies of cell viability, these data provide the first glimpse at the role of Bmx signaling in the normal and ischemic myocardium. These studies were supported by AHA and NIH/NHLBI grant funding.