[Show abstract][Hide abstract] ABSTRACT: Mounting evidence suggests that transplanting endothelial progenitor cells (EPCs) into the myocardium improves cardiac function after myocardial infarction (MI). However, the mechanism remains controversial. The aim of this study was to investigate the role played by the VEGF- PI3K/Akt-eNOS pathway in EPC-based cell therapy. Cultured EPCs, which were identified by morphology, function, and cell surface markers, were transplanted into the border zone after left anterior descending coronary artery ligation in mice. Expression levels of VEGF, p-Akt, and eNOS in the border zone were elevated three days after EPC transplantation. EPC therapy enhanced expression of VEGFR-2, increased microvessel density, and reduced interstitial fibrosis in the border zone after MI. The left ventricular fractional shortening was increased and the left ventricular diameter was smaller after EPC treatment. Wortmannin inhibited the expression of p-Akt and was associated with decreased cardiac function. Our study suggests that EPC transplantation improves cardiac function after MI, mediated at least partially by activation of the VEGF -PI3K/Akt-eNOS pathway.
Annals of clinical and laboratory science 11/2013; 43(4):395-401. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the usefulness of the routine sonographic evaluation of the pattern of fluctuate portal velocity tracings and the hepatic veins for the diagnosis of arterioportal fistula (APF) and cardiogenic trans-sinusoidal shunting (CTS). MATERIALS AND METHODS.: Color Doppler flow imaging and pulsed-wave Doppler (PW) examinations of the portal vein were performed in 282 subjects. The waveforms of the velocity tracings in the portal main trunk and its branches were determined to infer APF or CTS. Suspected cases of APFs or CTSs were always confirmed by echocardiography, contrast-enhanced ultrasound, computed tomography, or digital subtraction angiography findings. The portal maximum velocity (V(max)), minimum velocity(V(min)), V(max)/V(min), arterial peak systolic velocity and resistance index, and venous reverse and forward velocities were used to estimate their haemodynamics.
The waveform of the velocity tracing for the draining portal vein of APF was typically arterial-like or diphase, as indicated by a systolic hepatofugal dwarf peak and a diastolic hepatopetal low flat shape. The flow in the affected portal vein was always hepatofugal in an intrahepatic patient, whereas a hepatopetal flow was observed in an extrahepatic APF patient. The waveform of the velocity tracing for the portal vein of CTS patients, especially its intrahepatic branches, showed a typical hump-like shape with or without a transitory hepatofugal tracing. The PW results displayed an increase in the retrograde phase of the hepatic venous flow with increased velocities in the two phases.
Portal velocity tracings should be evaluated during routine detecting for APF or CTS, especially in patients with gastrointestinal upsets.
Radiology and Oncology 09/2012; 46(3):198-206. DOI:10.2478/v10019-012-0028-9 · 1.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial progenitor cells (EPCs) participate in vascular repair and angiogenesis. Thus, EPC transplantation into ischemic myocardium might improve cardiac function; however, the vast majority of cells die within a short period. The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the efficiency of EPC-based cell therapy.
Myocardial infarction was induced in wild-type mice by ligating the left anterior descending coronary artery. Enhanced green fluorescent protein-EPCs with or without EPO were transplanted into peri-infarct myocardium. Enhanced green fluorescent protein-EPCs were detected 7 and 28 d after surgery. The amount of circulating EPCs was analyzed 3 and 28 d after surgery. The stromal cell-derived factor-1α and vascular endothelial growth factor concentrations, microvessel density, apoptosis, fibrosis in the peri-infarct myocardium, and cardiac function were compared among the groups.
More enhanced green fluorescent protein-EPCs were found in the hearts treated with EPC + EPO than in those treated with EPC alone. The circulating EPC level was markedly elevated after EPC + EPO treatment compared with EPC application alone. Stromal cell-derived factor-1α and vascular endothelial growth factor were increased accordingly, along with increased microvessel density, decreased apoptosis, and reduced fibrosis in the peri-infarct myocardium. Left ventricular fractional shortening was greater and the interventricular septum was thicker after EPC + EPO treatment compared with EPC treatment alone.
EPO improved the efficiency of EPC therapy in mice with myocardial infarction. This effect was associated with enhanced transplanted EPC survival and autologous EPC mobilization.
Journal of Surgical Research 05/2012; 176(1):e47-55. DOI:10.1016/j.jss.2012.04.047 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Coronary revascularization has been well-established as the most effective treatment of limiting the eventual infarct size for coronary artery diseases. However, reperfusion can elicit a number of adverse reactions that may limit its beneficial actions. Although reduction of ischemia reperfusion (IR) injury through the use of antioxidant therapy, calcium-channel blockers, sodium-hydrogen exchange inhibitors, and antiinflammatory drugs has previously been attempted in many studies, few agents are clinically available for protecting the heart from IR injury . Activation of the pro-survival kinase-signaling cascade phosphatidylinositol 3-kinase (PI3K) /Akt at the time of reperfusion promotes cell survival and recruits the anti-apoptotic pathway during reperfusion . Experimental studies have indicated that the intervention and ischemia preconditioning of some pharmacological agents can recruit the PI3K/Akt pathway and confer powerful cardioprotection . It has been proposed that pharmacological targeting of the Akt pathway may potentially diminish IR injury . In a recent study , we reported that ligustrazine (2,3,5,6-tetramethylpyrazine,TMP), an alkaloid extracted from Ligusricum wallichii Franchat (Apiaceae), has cardioprotective effects against myocardial IR injury through limitation of infarct size and reduction of apoptosis. In this article, we further investigated whether the cardioprotective effect of TMP was dose-dependent through observing the ultrastructure, enzyme level, and oxidative stress of the myocardium and whether the PI3K/Akt signal pathway was involved in the cardioprotective effect of TMP using Western blot analysis.
Annals of clinical and laboratory science 03/2012; 42(2):198-202. · 0.91 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.
Clinical and Experimental Pharmacology and Physiology 01/2012; 39(1):20-7. DOI:10.1111/j.1440-1681.2011.05628.x · 2.37 Impact Factor