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ABSTRACT: BACKGROUND: So far, relatively few studies have addressed the use of stem cells to treat patients with refractory angina. Moreover, the results of current studies were discrepant. The objective of this meta-analysis was to evaluate the efficacy and safety of this treatment on a relatively large scale. METHODS: Studies were identified through PubMed, CENTRAL, EMBASE, reviews, and reference lists of relevant papers. The weighted mean difference was calculated with random-effect models for net changes in exercise tolerance and angina frequency, and odds ratio (OR) with fixed-effect models for myocardial infarction (MI) and death. RESULTS: Five randomized controlled trials, with a total of 381 patients, were included in the analysis. Compared with the controls, patients who received stem cell therapy had a significant improvement in exercise tolerance of 61.3 seconds (95% confidence interval [CI], 18.1-104.4; P = 0.005; I2 = 58%); an obvious reduction in angina frequency of 7.3 episodes per week (95% CI, -13.4 to -1.2; P = 0.02; I2 = 93%); and lower risk of MI, with an OR of 0.37 (95% CI, 0.14-0.95; P = 0.04; I2 = 0%). No difference was detected for the risk of death (OR, 0.33; 95% CI, 0.08-1.39; P = 0.13; I2 = 20%). CONCLUSIONS: Stem cell therapy appears to be effective and safe in the management of patients with refractory angina. The findings need confirmation in larger-scale studies with longer follow-up.
The Canadian journal of cardiology 03/2013; · 3.36 Impact Factor
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ABSTRACT: PURPOSE:: The objective of this study was to analyze the clinical characteristics of patients younger than 35 years with acute myocardial infarction (AMI). METHODS:: A total of 117 patients younger than 35 years with AMI admitted to the hospital during the recent 10 years were chosen, and 355 patients older than 65 years with AMI served as a control group. The case history, clinical data, coronary angiography and prognosis of the patients were analyzed and compared. RESULTS:: Among the younger patients with AMI, men (96.6%) and those smoking cigarettes (66.7%) account for the majority. ST-segment elevation (69.2%) and anterior wall infarction (43.6%) were more prevalent in the younger patients than in the older patients. Compared with the older patients, the younger patients had a higher level of low-density lipoprotein cholesterol (2.93 ± 1.48 versus 2.35 ± 1.21, P = 0.0428) and higher left ventricular ejection fraction (59.82 ± 10.86 versus 48.31 ± 12.48, P = 0.0396). Coronary angiography data showed that most of the younger patients were characteristic of having single-vessel lesion (66.7%), left anterior descending artery lesion (69.3%) and coronary artery spasm more than the older patients (6.8% versus 0.56%, P = 0.0001). In addition, the in-hospital mortality, and the prognosis after 1 and 12 months in the younger patients were comparatively better. CONCLUSIONS:: The main risk factors for young adults aged <35 years with AMI include cigarette smoking, hyperlipidemia and family history of coronary artery disease, and smoking cessation and lifestyle improvement are important considerations for the prevention of this disease in this population.
The American Journal of the Medical Sciences 01/2013; · 1.39 Impact Factor
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ABSTRACT: Stem cell-based therapy is a promising option for the treatment of ischemic heart diseases. As to a successful stem cell-based therapy, one of the most important issues is that the stable engraftment and survival of implanted stem cells in cardiac microenvironment. There are evidences suggest that pharmacological treatment devoted to regulate stem cell function might represent a potential new therapeutic strategy and are drawing nearer to becoming a part of treatment in clinical settings. Statins could exert cholesterol-independent or pleiotropic effects to cardiovascular system. Recent studies have shown that statins could modulate the biological characteristics and function of various stem cells, thus could be an effective method to facilitate stem cell therapy. This review will focus on statins and their modulation effects on various stem cells.
Ageing research reviews 04/2012; 12(1):1-7. · 5.62 Impact Factor
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ABSTRACT: Autophagy is a complex "self-eating" process and could be utilized for cell survival under stresses. Statins, which could reduce apoptosis in mesenchymal stem cells (MSCs) during both ischemia and hypoxia/serum deprivation (H/SD), have been proved to induce autophagy in some cell lines. We have previously shown that atorvastatin (ATV) could regulate AMP-activated protein kinase (AMPK), a positive modulator of autophagy, in MSCs. Thus, we hypothesized that autophagy activation through AMPK and its downstream molecule mammalian target of rapamycin (mTOR) may be a novel mechanism of ATV to protect MSCs from apoptosis during H/SD. Here, we demonstrated that H/SD induced autophagy in MSCs significantly as identified by increasing acidic vesicular organelle-positive cells, type II of light chain 3 (LC3-II) expression, and autophagosome formation. The levels of H/SD-induced apoptosis were increased by autophagy inhibitor 3-methyladenine (3-MA) while decreased by rapamycin, an autophagic inducer. ATV further enhanced the autophagic activity observed in MSCs exposed to H/SD. Treatment with 3-MA attenuated ATV-induced autophagy and abrogated the protective effects of ATV on MSC apoptosis, while rapamycin failed to cause additional effects on either autophagy or apoptosis compared with ATV alone. The phosphorylation of AMPK was upregulated whereas the phosphorylation of mTOR was downregulated in ATV-treated MSCs, which were both attenuated by AMPK inhibitor compound C. Further, treatment with compound C reduced the ATV-induced autophagy in MSCs under H/SD. These data suggest that autophagy plays a protective role in H/SD-induced apoptosis of MSCs, and ATV could effectively activate autophagy via AMPK/mTOR pathway to enhance MSC survival during H/SD.
Stem cells and development 02/2012; 21(8):1321-32. · 4.15 Impact Factor
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ABSTRACT: The effect of mesenchymal stem cells (MSCs) transplantation is poor because of the harsh environment post infarction. Our previous studies have proven that Statins could enhance the implanted bone marrow MSCs survival, but the exact mechanism remained to be clarified. We hypothesized that atorvastatin (Ator) could protect MSCs from hypoxia and serum-free (H/SF) induced apoptosis and investigated the potential mechanisms.
Chinese mini-swine's bone marrow derived MSCs were cultured in vitro and exposed to hypoxia and H/SF, Ator of various concentrations (0.001 - 10 µmol/L), AMPK inhibitor-compound C (CC), PI3K inhibitor-LY294002 (LY), Ator + CC and Ator + LY. Cell apoptosis was assessed using Annexin V/Propidine Iodine kit by flow cytometry. Phosphorylation of AMPK, Akt, endothelial nitric oxide synthase (eNOS) level and phosphorylation were tested with Western blot. Real Time-PCR was performed to analyze the gene expression of AMPK, Akt and eNOS.
MSCs apoptosis in Ator (0.01 - 10 µmol/L) treated H/SF groups was significantly reduced compared with H/SF group (1.94% - 6.10% vs. 10.94%, P < 0.01 or 0.05). Apoptosis was higher in Ator + CC group than in 1 µmol/L Ator group (4.94% ± 0.98% vs. 2.59% ± 0.84%, P < 0.01) and similar between Ator + LY and 1 µmol/L Ator group (2.02% ± 0.45% vs. 2.59% ± 0.84%, P > 0.05). The gene expressions of AMPK, Akt and eNOS were significantly upregulated in atorvastatin treated groups. Meanwhile, phosphorylation of AMPK and eNOS increased in MSCs treated with atorvastatin (P < 0.01 or 0.05). Phosphorylation of eNOS significantly correlated with AMPK phosphorylation (r = 0.599, P = 0.004), but not with Akt phosphorylation (P = 0.263).
Atorvastatin can protect MSCs from H/SF induced apoptosis through AMPK pathway, which resulting in activation of eNOS.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 11/2011; 39(11):1033-8.
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ABSTRACT: Ischemia and ischemia/reperfusion can dephosphorylate and redistribute connexin 43 (Cx43). But it is unknown whether no-reflow phenomenon has an effect on the expression and distribution of Cx43 after acute infarction and reperfusion.
21 open-chest pigs were divided into three groups. Left anterior descending artery (LAD) occlusion for 90 min before 180 min of reperfusion was made in ischemia/reperfusion group. The pigs in ischemia groups were either subjected to LAD ligation for 90 min or for 270 min. No-reflow and risk regions were determined pathologically by dye staining. Cx43 expression was measured by western blotting and quantitative RT-PCR analysis. Cx43 spatial distribution was shown by immunofluorescence examination.
The content of phosphorylated and mRNA of Cx43 were higher in reflow region than in the no-reflow or sustained ischemic region. The distribution of Cx43 was also altered in no-reflow region.
There are some differences in synthesis, expression and distribution of myocardial Cx43 at microvascular level after ischemia/reperfusion. Cx43 is partially rephosphorylated with reperfusion only in the reflow myocardium.
Microvascular Research 07/2011; 82(3):404-9. · 2.83 Impact Factor
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ABSTRACT: Resveratrol is a well-known antioxidant that exists in grape skin/seed, red wine, and the root of Polygonum cuspidatum, a traditional Chinese and Japanese medicinal material. Studies have found that resveratrol has many interesting properties, including anti-carcinogenic properties, anti-microbial and antiviral effects, the ability to reverse dyslipidemia and obesity, the ability to attenuate hyperglycemia and hyperinsulinemia, and the ability to protect endothelial function. Heart failure is the final consequence of the majority of cardiovascular diseases, and resveratrol has been shown to directly attenuate heart contraction. The cardiovascular protective capacities of resveratrol are associated with multiple molecular targets and may lead to the development of novel therapeutic strategies for atherosclerosis, ischemia/reperfusion, metabolic syndrome, and heart failure. This article will mainly review recently published basic researches about the protective cardiovascular effects of resveratrol because these results may lead to the development of new clinical therapeutics in patients.
Heart Failure Reviews 06/2011; 17(3):437-48. · 3.20 Impact Factor
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ABSTRACT: Widespread death of implanted cells hampers the development of stem cell therapy for acute myocardial infarction (AMI). Our previous studies indicated that statins can protect implanted mesenchymal stem cells (MSCs) against the post-infarct microenvironment, thus increasing the therapeutic effect. However, the underlying mechanisms are unclear. The JAK-STAT pathway participates in regulation of stress responses of the myocardium to various insults. This study aimed to detect whether rosuvastatin (ROSU) facilitates the survival, engraftment, and differentiation of allogeneic bone marrow-derived MSCs in the post-infarct heart via the JAK-STAT signaling pathway.
Female Sprague-Dawley rats were randomized into 5 groups: AMI (control), ROSU gavage (group R), MSCs transplantation (group M), MSCs and ROSU (group M+R), or MSCs, ROSU and a JAK2 inhibitor AG-490 (group M+R+AG). MSCs from male rats were injected into the myocardium 1 week after AMI. Cardiac function and histology, as well as the expression of Y-chromosomal genes and JAK-STAT signaling proteins, were examined at 4 weeks after transplantation. Better functional recovery, increased survival and differentiation of MSCs occurred in group M+R. Furthermore, phosphorylation of JAK2 and STAT3 was higher in group M+R. The effects of ROSU, as well as of activated JAK-STAT proteins, could be attenuated by AG-490.
ROSU treatment improves the efficacy of stem cell transplantation in infarcted hearts by activation of the JAK2-STAT3 signaling pathway.
Circulation Journal 05/2011; 75(6):1476-85. · 3.77 Impact Factor
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Xiang-Dong Li,
Yue-Jin Yang,
Yong-Jian Geng,
Chen Jin,
Feng-Huan Hu,
Jing-Lin Zhao,
Hai-Tao Zhang,
Yu-Tong Cheng, Hai-Yan Qian,
Lin-Lin Wang,
Bao-Jie Zhang,
Yi-Ling Wu
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ABSTRACT: The objective of the present study was to investigate whether pretreatment with single low loading dose of tongxinluo (TXL), a traditional Chinese medicine, 1 h before myocardial ischemia could attenuate no-reflow and ischemia-reperfusion injury by regulating endothelial nitric oxide synthase (eNOS) via the PKA pathway. In a 90-min ischemia and 3-h reperfusion model, minipigs were randomly assigned to the following groups: sham, control, TXL (0.05 g/kg, gavaged 1 h before ischemia), TXL + H-89 (a PKA inhibitor, intravenously infused at a dose of 1.0 μg·kg(-1)·min(-1) 30 min before ischemia), and TXL + N(ω)-nitro-L-arginine (L-NNA; an eNOS inhibitor, intravenously administered at a dose of 10 mg/kg 30 min before ischemia). TXL decreased creatine kinase (CK) activity (P < 0.05) and reduced the no-reflow area from 48.6% to 9.5% and infarct size from 78.5% to 59.2% (P < 0.05), whereas these effects of TXL were partially abolished by H-89 and completely reversed by L-NNA. TXL elevated PKA activity and the expression of PKA, Thr(198) phosphorylated PKA, Ser(1179) phosphorylated eNOS, and Ser(635) phosphorylated eNOS in the ischemic myocardium. H-89 repressed the TXL-induced enhancement of PKA activity and phosphorylation of eNOS at Ser(635), and L-NNA counteracted the phosphorylation of eNOS at Ser(1179) and Ser(635) without an apparent influence on PKA activity. In conclusion, pretreatment with a single low loading dose of TXL 1 h before ischemia reduces myocardial no-reflow and ischemia-reperfusion injury by upregulating the phosphorylation of eNOS at Ser(1179) and Ser(635), and this effect is partially mediated by the PKA pathway.
AJP Heart and Circulatory Physiology 10/2010; 299(4):H1255-61. · 3.71 Impact Factor
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ABSTRACT: In recent years, stem cell-based therapy has been given increased attention in terms of its potential contribution to cardiac regeneration and repair, after acute myocardial infarction (AMI). The published studies have identified many kinds of stem cells with the ability to regenerate and repair damaged myocardium after AMI. These include embryonic stem cells (ESCs), mesenchymal stem cells (MSCs), multipotent adult progenitor cells, unrestricted somatic stem cells, etc. More recently, very small embryonic-like stem cells (VSELs) were identified from murine, as a population of very small CXCR4(+) Lin(-) CD45(-) cells and from human, as a population of very small CD34(+) CD133(+) CXCR4(+) Lin(-) CD45(-) cells. These cells exhibit beneficial effects on improving cardiac function and attenuating cardiac remodeling after AMI. However, the mechanisms underlying the benefits associated with VSELs therapy, in cardiac regeneration and repair, remain poorly understood. This review summarizes the current studies on cardiac repair with VSELs after AMI, and discusses the potential mechanisms and implications of these cells in cardiac repair.
Ageing research reviews 10/2010; 10(1):173-7. · 5.62 Impact Factor
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Ji Huang, Hai-Yan Qian,
Zhi-Zhong Li,
Jing-Mei Zhang,
Su Wang,
Ying Tao,
Yu-Long Gao,
Cheng-Qian Yin,
Bin Que,
Tao Sun,
Zhan-Yong Zhao,
Zhao Li
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ABSTRACT: Endothelial lipase, which is a newly identified member of the lipase family, plays an important role in high-density lipoprotein metabolism, which catalyzes the hydrolysis of high-density lipoprotein phospholipids and facilitates the clearance of high-density lipoprotein from the circulation. In addition, inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1beta), upregulate endothelial lipase expression, and endothelial lipase also affects the expression of cytokines, which in turn play an important role in atherogenesis. Endothelial lipase expression has been associated with macrophages within human atherosclerotic lesions. However, an important challenge is to determine how endothelial lipase alters the progression of atherosclerosis. Although few data are available from human studies, it seems that plasma endothelial lipase levels in individuals with atherosclerosis might be higher than that measured in healthy individuals. Therefore, we believe that endothelial lipase might be a promising marker for atherosclerosis in clinical settings in the future.
Translational research : the journal of laboratory and clinical medicine. 07/2010; 156(1):1-6.
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ABSTRACT: To observe in vivo stem cell distribution and viability after transplantation by noninvasive imaging of 18F-fluorodeoxyglucose (18F-FDG) labeled autologous mononuclear bone marrow cells.
Myocardial infarction was established in 8 swine by ligating left anterior descending coronary artery after anesthesia. Bone marrow (20 ml) was drawn through ileum. After isolation, mononuclear bone marrow cells were labeled by radionuclide 18F-FDG and intramyocardially injected into infarction region. Whole body planar scan and myocardial tomography scan were performed immediately, 1 h, 2 h, and 3 h post stem cell injection. Viability and stability of radionuclide labeled stem cells were determined at 3 h post labeling in vitro.
The labeling efficiency was (67 +/- 14)%. Mean dose of radioactive in marrow cells was (32 +/- 7) MBq. Trypan blue staining showed in vitro viability was (95 +/- 3)% at 3 h post labeling. After intramyocardial injection, labeled mononuclear bone marrow cell retention rate in infarction region was (83 +/- 6)%, (49 +/- 8)%, (32 +/- 6)% and (24 +/- 5)% immediately, 1 h, 2 h, and 3 h post injection, respectively.
Distribution and viability of stem cell after cardiac transplantation could be effective monitored by 18F-FDG labeled autologous mononuclear bone marrow cell technique in acute stage in this model.
Zhonghua xin xue guan bing za zhi [Chinese journal of cardiovascular diseases] 06/2010; 38(6):545-8.
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ABSTRACT: Widespread death of implanted cells hampers stem cell therapy for acute myocardial infarction (AMI). Based on the pleiotropic beneficial effects of statins, we examined whether simvastatin (SIMV) increased the efficacy of mesenchymal stem cell (MSC) transplantation after AMI.
Chinese miniswine (n=28) were randomized to 1 of 4 groups (n=7 per group): control, SIMV (0.25 mg/kg x d), MSC transplantation, and SIMV+MSCs. AMI was created by ligating the left anterior descending coronary artery; MSCs were injected immediately into the cyanotic myocardium. At 6 weeks, MRI showed the number of dyskinetic segments and the infarct size were significantly decreased in the SIMV group. Cardiac function improved and the perfusion defect decreased significantly in the SIMV+MSC group but not in the MSC-only group (P<0.05, versus control group). MSC survival and differentiation were significantly better in the combination group than in the MSC-only group (P<0.01). Cell apoptosis decreased significantly in both the SIMV and the SIMV+MSC groups but not in the MSC-only group when compared with controls (P<0.05). Furthermore, oxidative stress and inflammatory response was significantly reduced in the infarcted regions in both the SIMV and the SIMV+MSCs groups.
SIMV treatment improves the therapeutic efficacy of MSC transplantation in acutely infarcted hearts by promoting cell survival and cardiovascular differentiation.
Arteriosclerosis Thrombosis and Vascular Biology 09/2009; 29(12):2076-82. · 6.37 Impact Factor
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ABSTRACT: The traditional Chinese medicine Tongxinluo can protect myocardium against ischaemia/reperfusion injury, but the mechanism of its action is not well documented. We examined the involvement of nitric oxide in the protective role of Tongxinluo.
Miniswine were randomized to four groups of seven: sham, control, Tongxinluo and Tongxinluo coadministration with a nitric oxide synthase inhibitor N(omega)-nitro-L-arginine (L-NNA, 10 mg/kg i.v.). Three hours after administration of Tongxinluo, the animals were anaesthetised and the left anterior descending coronary artery ligated and maintained in situ for 90 minutes followed by 3 hours of reperfusion before death. Area of no reflow and necrosis and risk region were determined pathologically by planimetry. The degree of neutrophil accumulation in myocardium was obtained by measuring myeloperoxidase activity and histological analysis. Myocardial endothelial nitric oxide synthase activity and vascular endothelial cadherin content were measured by colorimetric method and immunoblotting analysis respectively.
Tongxinluo significantly increased the local blood flow and limited the infarct and size of no reflow. Tongxinluo also attenuated myeloperoxidase activity and neutrophil accumulation in histological sections and maintained the level of vascular endothelial cadherin and endothelial nitric oxide synthase activity in the reflow region when compared with control group. The protection of Tongxinluo was counteracted by coadministration with L-NNA.
Tongxinluo may limit myocardial ischaemia and protect the heart against reperfusion injury. Tongxinluo regulates synthesis of nitric oxide by altering activity of endothelial nitric oxide synthase.
Chinese medical journal 08/2009; 122(13):1529-38. · 0.86 Impact Factor
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Yue-Jin Yang, Hai-Yan Qian,
Ji Huang,
Yong-Jian Geng,
Run-Lin Gao,
Ke-Fei Dou,
Guo-Sheng Yang,
Jian-Jun Li,
Rui Shen,
Zuo-Xiang He,
Min-Jie Lu,
Shi-Hua Zhao
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ABSTRACT: To investigate whether Atorvastatin (Ator) treatment improves the cardiac micro-environment that facilitates survival and differentiation of bone-marrow-derived mesenchymal stem cells (MSCs) implanted in the post-infarct myocardium.
Myocardial infarction was created by coronary ligation and immediately after reperfusion, autologous bone-marrow-derived MSCs were transplanted into the hearts of Chinese swine that were pretreated with or without Ator. Six weeks after transplantation, as evaluated by SPECT and MRI all the animals with Ator showed improved cardiac perfusion and contractility when compared with untreated. Increased survival and differentiation of implanted MSCs and decreased infarct area were observed in the Ator-treated, MSC-implanted animals. In the absence of Ator, MSC transplantation only achieved a modest improvement in perfusion and morphology. The combined treatment with Ator and MSCs significantly inhibited cardiac cell apoptosis, reduced oxidative stress, and suppressed expression of the inflammatory cytokines in the post-infarct myocardium.
Ator treatment may protect the myocardium undergoing acute infarction and reperfusion by creating a better environment for the survival and differentiation of implanted MSCs. The benefit of the Ator/stem cell combined therapy may result from the statin-mediated inhibition of apoptosis, oxidative stress, and inflammation in the infarcted myocardium.
European Heart Journal 07/2008; 29(12):1578-90. · 10.48 Impact Factor
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Hai-yan Qian,
Yue-jin Yang,
Ji Huang,
Run-lin Gao,
Ke-fei Dou,
Guo-sheng Yang,
Jian-jun Li,
Rui Shen,
Zuo-xiang He,
Min-jie Lu,
Shi-hua Zhao
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ABSTRACT: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion.
Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint.
At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL.
Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.
Chinese medical journal 08/2007; 120(16):1416-25. · 0.86 Impact Factor
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ABSTRACT: Peripheral arterial disease (PAD) includes a wide range of manifestations in the lower limb, from asymptomatic to symptomatic disease ranging from intermittent claudication to critical limb ischemia, with ulcers, rest pain, or gangrene. It is manifestation of generalized atherosclerosis and this is clearly shown by the high prevalence of coexistence coronary and cerebral arterial disease in these patients. The cumulative findings on molecular and cellular biology have dramatically changed our concept of atherosclerotic disease. Recently, it has become clear that inflammation is fundamental to the process of atherosclerosis. Although the relation between inflammation and PAD is not well characterized, the emerging data demonstrated that PAD is a common manifestation of atherosclerosis that is associated with a systemic inflammation. The most important risk factors for PAD are similar to those of atherosclerotic disease elsewhere: age, male sex, diabetes mellitus, smoking, hypertension, hyperlipidemia, and hereditary factors. Serum levels of inflammatory markers, especially after exercise, have been found to be higher in patients with PAD than in controls, and associated with prognosis as well as restenosis in patients with PAD after revascularization. In the general United States adult population, inflammation is independently associated with PAD in a cross-sectional, nationally large representative sample. All of those evidences indicate that PAD is one aspect of atherosclerosis, a disease rationally connects with inflammation, which may further change our preventive and therapeutic strategies.
Medical Hypotheses 02/2007; 69(6):1190-5. · 1.39 Impact Factor
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ABSTRACT: Myocardial infarction is the leading cause of congestive heart failure and death in the industrialized world. However, the intrinsic repair mechanism of the injured heart and current therapeutic means are inadequate to regenerate lost myocardium. Recent interests focused on cellular cardiomyoplasty which is an outside intervention to support the reparative process in the heart through transplantation of stem/progenitor cells. Cellular myocardioplasty with stem cells is a possible option to reverse the adverse hemodynamic and neurohormonal imbalance after myocardial infarction. Experimental studies and clinical trials suggest that cellular cardiomyoplasty with stem/progenitor cells may improve cardiac function and prevent ventricular remodeling of the injured heart. Although the mechanisms are still in intensive debate, cellular cardiomyoplasty with stem cells has already been introduced into the clinical settings. However, it is an important challenge how donor cells are delivered to the targeted area. In early studies in animals, intramyocardial injection of stem cells after thoracotomy is the main transplantation route which is not suitable to most patients in clinical settings. Then the catheter-based infusion of stem cells is clinically introduced and rapidly developed because of its safety, convenience and micro-invasion. We hypothesize that catheter-based transplantation with stem cells may be a promising means to treat ischemic heart diseases in the future in clinical settings.
Medical Hypotheses 02/2007; 69(6):1212-8. · 1.39 Impact Factor
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ABSTRACT: Cardiac syndrome X is defined as a typical angina pectoris, positive treadmill exercise test, negative intravenous ergonovine test and normal coronary angiography. The pathogenesis of cardiac syndrome X has previously ascribed to myocardial ischemia that may be caused by microvascular dysfunction and increased sensitivity to intracardiac pain. Despite the extensive studies, the pathophysiological mechanisms in cardiac syndrome, however, remain unclear. More recently, the data has been suggested that chronic inflammation has been associated with cardiac syndrome X. The evidence for the hypotheses included that inflammatory marker are increased, and associated with the disease activity in patients with cardiac syndrome X. And also, statin, a lipid-lowering as well as anti-inflammatory drug, has significantly modified the disease process in this special syndrome. Despite the good prognosis of cardiac syndrome X, the chronic, frequent nature of the persistent angina and reduced exercise tolerance can significantly impair quality of life. Thus, lowering inflammatory response by, for example, use of statin and/or aspirin, might improve coronary microvascular dysfunction. Whether this is a valid approach, however, is still unknown and deserves further investigation. Indeed, as mediators of inflammation are multiple, the strategy of identifying triggers and mechanisms of inflammation in each special clinical setting and directing treatment at the special triggers or to rate limiting steps in effector pathways appears more reasonable or a promising strategy.
Medical Hypotheses 02/2006; 66(1):87-91. · 1.39 Impact Factor
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ABSTRACT: The evidence has indicated that rapid reduction of inflammatory marker, such as C-reactive protein (CRP) could be achieved by administration of a statin. However, limited information is available in evaluating the short-term time course of CRP reduction in patients with coronary artery disease by use of a statin. Forty-two patients with stable angina were randomly assigned to 20 mg/d or 40 mg/d group of pravastatin. Blood samples were drawn at days 0, 1, and 14 for measuring lipid profile, CRP levels, and hepatic enzymes in all patients. The results showed that both doses of pravastatin induced significant reductions in median CRP levels and in mean CRP levels, respectively, at day 1 (20% in the 20 mg/d group and 17.6% in the 40 mg/d group; 15% in the 20 mg/d group and 10% in the 40 mg/d group) as well as at day 14 (28.6% in the 20 mg/d group and 33.3% in the 40 mg/d group; 25% in the 20 mg/d group and 22.8% in the 40 mg/d group) compared with baseline data without a dose-dependent manner. In addition, no changes were found at day 1 regarding lipid profile; however, both doses of pravastatin induced significant reductions in total cholesterol (TC, 22% and 30%), and low-density lipoprotein (LDL) cholesterol (30% and 40%) compared with baseline at 14 days. The higher dose of pravastatin resulted in significantly greater reductions in TC and LDL cholesterol compared with the 20 mg/d dose (p = 0.05, p = 0.01, respectively). A less significant reduction was observed in triglycerides level (16% and 24%) compared with TC and LDL cholesterol. There was no significant difference in mean high-density lipoprotein (HDL) cholesterol levels compared with baseline in both groups. These data suggested that a common daily dose of pravastatin resulted in rapid reduction of CRP within 24 hours and of lipid profile within 2 weeks, and the benefit to the vascular endothelium might occur quickly by reduction of CRP levels, which may be clinically important for patients in a high-risk subgroup, such as acute coronary artery disease.
Angiology 57(1):1-7. · 1.51 Impact Factor
