Acute erythropoietin cardioprotection is mediated by endothelial response
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Ruifeng Teng John W. Calvert Nathawut Sibmooh Barbora Piknova Norio Suzuki Junhui Sun Kevin Martinez Masayuki Yamamoto Alan N. Schecht
- چاپ و سال / کشور: 2011
Description
Increasing evidence indicates that high levels of serum erythropoietin (Epo) can lessen ischemia–reperfusion injury in the heart and multiple cardiac cell types have been suggested to play a role in this Epo effect. To clarify the mechanisms underlying this cardioprotection, we explored Epo treatment of coronary artery endothelial cells and Epo cardioprotection in a Mus musculus model with Epo receptor expression restricted to hematopoietic and endothelial cells (DEpoR). Epo stimulation of coronary artery endothelial cells upregulated endothelial nitric oxide synthase (eNOS) activity in vitro and in vivo, and enhanced nitric oxide (NO) production that was determined directly by real-time measurements of gaseous NO release. Epo stimulated phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) and mitogen-activated protein kinase kinase (MEK)/extracellular signal regulated kinase (ERK) signaling pathways, and inhibition of PI3K, but not MEK activity, blocked Epo-induced NO production. To verify the potential of this Epo effect in cardioprotection in vivo, DEpoR-mice with Epo response in heart restricted to endothelium were treated with Epo. These mice exhibited a similar increase in eNOS phosphorylation in coronary artery endothelium as that found in wild type (WT) mice. In addition, in both WT- and DEpoR-mice, exogenous Epo treatment prior to myocardial ischemia provided comparable protection. These data provide the first evidence that endothelial cell response to Epo is sufficient to achieve an acute cardioprotective effect. The immediate response of coronary artery endothelial cells to Epo stimulation by NO production may be a critical mechanism underlying this Epo cardioprotection
Basic Res Cardiol (2011) 106:343–354 Received: 3 January 2011 / Revised: 25 January 2011 / Accepted: 25 January 2011 / Published online: 23 February 2011
