Erythropoietin attenuates cardiac dysfunction by increasing myocardial angiogenesis and inhibiting interstitial fibrosis in diabetic rats

Abstract

BackgroundRecent studies revealed that erythropoietin (EPO) has tissue-protective effects in the heart by increasing vascular endothelial growth factor (VEGF) expression and attenuating myocardial fibrosis in ischemia models. In this study, we investigated the effect of EPO on ventricular remodeling and blood vessel growth in diabetic rats.MethodsMale SD rats were randomly divided into 3 groups: control rats, streptozotocin (STZ)-induced diabetic rats, and diabetic rats treated with 1000 U/kg EPO by subcutaneous injection once per week. Twelve weeks later, echocardiography was conducted, and blood samples were collected for counting of peripheral blood endothelial progenitor cells (EPCs). Myocardial tissues were collected, quantitative real-time PCR (RT-PCR) was used to detect the mRNA expression of VEGF and EPO-receptor (EPOR), and Western blotting was used to detect the protein expression of VEGF and EPOR. VEGF, EPOR, transforming growth factor beta (TGF-β), and CD31 levels in the myocardium were determined by immunohistochemistry. To detect cardiac hypertrophy, immunohistochemistry of collagen type I, collagen type III, and Picrosirius Red staining were performed, and cardiomyocyte cross-sectional area was measured.ResultsAfter 12 weeks STZ injection, blood glucose increased significantly and remained consistently elevated. EPO treatment significantly improved cardiac contractility and reduced diastolic dysfunction. Rats receiving the EPO injection showed a significant increase in circulating EPCs (27.85 ± 3.43%, P < 0.01) compared with diabetic untreated animals. EPO injection significantly increased capillary density as well as EPOR and VEGF expression in left ventricular myocardial tissue from diabetic rats. Moreover, EPO inhibited interstitial collagen deposition and reduced TGF-β expression.ConclusionsTreatment with EPO protects cardiac tissue in diabetic animals by increasing VEGF and EPOR expression levels, leading to improved revascularization and the inhibition of cardiac fibrosis.

Pleiotropic and Renoprotective Effects of Erythropoietin Beta on Experimental Diabetic Nephropathy Model

“…Lu et al [24] reported that epoetin beta inhibits cardiac fibrosis in the experimental diabetes model. Recently, Geng et al [25] reported that epoetin ameliorates renal interstitial fibrosis in the experimental unilateral ureteral obstruction model.…”

TT‑1, an analog of melittin, triggers apoptosis in human thyroid cancer TT cells via regulating caspase, Bcl‑2 and Bax

“…The effects of TT-1 on the Bax, Bcl-2, caspase-3 and caspase-9 RNA expression in TT cells were examined by RT-qPCR as previously described (25,26). Total RNA was extracted from TT cells with or without TT-1 treatment (0-8 µg/ml for 48 h) by using Trizol reagent and then purified with an RNeasy Mini kit (Qiagen GmbH, Hilden, Germany).…”

Physiologic Remote Ischemic Training Offers a Cardioprotective Effect against Myocardial Infarction in a Time-Dependent Manner

“…For capillary density measurement, endothelial cells were stained with CD31, which is often used as a biological marker to represent capillary vessels in the myocardium [17]. Immunohistochemistry was performed using rabbit anti-rat CD31 antibody (Santa Cruz Biotechnology, USA, 1:100), and the staining was visualized by reaction with DAB (Sigma Chemical Co., USA, 1:20).…”

“…Immunohistochemistry was performed using rabbit anti-rat CD31 antibody (Santa Cruz Biotechnology, USA, 1:100), and the staining was visualized by reaction with DAB (Sigma Chemical Co., USA, 1:20). Capillaries were identified by a brown round structure with a central lumen and a diameter <20μm and a layer of endothelial cells without smooth muscle cells in the myocardium under a light microscope (magnification, 400X) (17) . Five fields on the slide were randomly chosen for counting the stained capillaries.…”