A novel protective effect of erythropoietin in the infarcted heart

Abstract

Erythropoietin (EPO) has been shown to protect neurons from ischemic stroke, but can also increase thrombotic events and mortality rates in patients with ischemic heart disease. We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart. We show that preconditioning with EPO protects H9c2 myoblasts in vitro and cardiomyocytes in vivo against ischemic injury. EPO treatment leads to significantly improved cardiac function following myocardial infarction. This protection is associated with mitigation of myocyte apoptosis, translating into more viable myocardium and less ventricular dysfunction. EPO-mediated myocyte survival appears to involve Akt activation. Importantly, cardioprotective effects of EPO were seen without an increase in hematocrit (eliminating oxygen delivery as an etiologic factor in myocyte survival and function), demonstrating that EPO can directly protect the ischemic and infarcted heart. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: myocardial infarction (MI); erythropoietin (EPO); erythropoietin receptor (EPO-R); Janus-associated kinase-2 (Jak2); trichloroacetic acid (TCA); left circumflex coronary artery (LCx); reactive oxygen species (ROS); left ventricle (LV); triphenyltetrazolium chloride (TTC); β-adrenergic receptor (βAR); LV end-diastolic pressure (LVEDP).

Attenuation of Interstitial Inflammation and Fibrosis by Recombinant Human Erythropoietin in Chronic Cyclosporine Nephropathy

“…However, rHuEPO treatment for 1 week also decreased macrophage infiltration, proinflammatory mediator (CRP), and profibrotic cytokine (TGF-β1 mRNA) expression without affecting Hb and Hct levels. This finding suggests that a direct effect of rHuEPO as well as improvement of hematopoiesis is responsible for protection against CsA-induced renal injury, which was previously demonstrated in the heart [14], CNS [15,16,17,18,19,20,21], and kidney [22,23,24]. …”

“…First of all, our study was focused on the effect of rHuEPO on apoptotic cell death since rHuEPO is a well-known anti-apoptotic agent against noxious or ischemic injury in various organs [14, 16, 18, 41, 42], and that apoptotic cell death plays a role in the pathogenesis of chronic CsA nephropathy [43,44,45]. The results of this study showed that rHuEPO significantly decreased the number of TUNEL-positive cells, which increased in CsA-treated rat kidneys.…”

“…Recently, the functions of rHuEPO have extended to cytoprotection [12,13,14,15]. Examples of this include protection against neuronal ischemia [16,17,18], traumatic injury [19], subarachnoid hemorrhage [20], and excitotoxins [21].…”

Cardiac adenoviral S100A1 gene delivery rescues failing myocardium

“…Sham-OP control animals (n = 9) underwent a similar procedure except that cryoprobes were not applied. Hearts of 6 cryoinfarcted animals were sectioned transaxially, and size of the infarcted LV area as a percent of total LV area was estimated to 32% ± 3% by triphenyltetrazolium chloride (TTC) staining ( Figure 1A) (22). There were no differences in infarct size between any subsequent groups (data not shown).…”

Chronic Erythropoietin Treatment Decreases Post-Infarct Myocardial Damage in Rats without Venous Thrombogenic Effect

“…Several studies have recently demonstrated that recombinant human erythropoietin (EPO) was effective in the protection of the myocardium against ischemic injury [1,2,3,4,5,6,7]. A single injection of a high dose of EPO (1,000–5,000 U/kg), 12–24 h before ischemia-reperfusion, has been shown to confer preconditioning protection on the heart, preventing cardiomyocyte apoptosis and cardiac dysfunction [5, 8].…”