Dilated Cardiomyopathy, Myocardial And Vascular Injury And Repair Mechanisms

Background:Stem cell transplantation had beneficial effects in dilated cardiomyopathy.However,heart distribution of transplanted stem cell and the mechanism of stem cell homing to cardiac tissue in dilated cardiomyopathy have not yet been reported.Methods:Mesenchymal stem cells(MSCs)were obtained from rat bone marrow,expanded in vitro,analyzed by fluorescenced-activated cell sorting(FACS),and labeled with ^99mTcO₄^-.DCM model was induced by the intraperitoneal administration of doxorubicin(total dose 15 mg/kg)in rat. ^99mTcO₄^- labeled cells were infused into the left ventricular of DCM and control rats.Sixteen hours after injection of MSC, animals were killed and different tissues were harvested to measure specific radioactivity.By real-time polymerase chain reaction(PCR)and immunohistochemistry,SDF-1 mRNA and protein expression of cardiac myocytes were measured.Results:Labeling efficiency of MSC was 70±11.2%.Viability and function were unchanged compare to unlabeled cells according to trypan-blue staining and readhering to culture plate and proliferate.Sixteen hours after MSC transplantation, the heart-to-muscle radioactivity ratio was increased significantly in DCM hearts compare to control hearts(12.98±1.22 vs 10.17±1.45,P＜0.05).The relative amount of SDF-1 protein expression was upregulated in DCM hearts compared with control hearts.SDF-1 mRNA expression was upregulated from 0.33±0.13 in control hearts to 0.47±0.12 in DCM hearts(P＜0.05).Conclusion:The increased SDF-1 expression in DCM myocardium is relevant to enhance the recruitment of implanted stem cell to DCM heart induced by doxorubicin. Objective: To investigate the relationship between soluble intercellular adhesion molecule-1 (sICAM-1) and artery compliance and cardiac function in dilated cardiomyopathy (DCM).Methods: Sixty-five DCM patients (aged 50.5±13.9) and forty-nine healthy volunteers (aged 50.1±8.1) were enrolled in the study. Serum concentrations of ICAM-1 were analyzed by quantitative enzyme-linked immunosorbent assays (ELISAs). The severity of heart failure was assessed in accordance to the New York Heart Association (NYHA)-classification. Both large artery compliance (C₁) and small artery compliance (C₂) were measured with the CVProfilor DO-2020.Results: (1) Serum ICAM-1 levels were significantly higher in DCM patients compared to controls (186.1±89.9ng/ml vs 98.8±57.7ng/ml P < 0.0001). Although C₂ was significantly lower in DCM patients than controls (3.8±1.8 ml/mmHg×100 vs 5.0±2.2 ml/mmHg×100, P < 0.0001), C₁ remained unchanged in comparison with the control group. (2) sICAM-1 levels were elevated with the decreasing cardiac function and there was rank correlation between sICAM-1 and cardiac function (r_s=0.425, P < 0.05). sICAM-1 was inversely correlated with C₂ in DCM patients (r=-0.55 P < 0.001). (3) Multivariate regression analysis showed that sICAM-1 was the main risk factor for C₂.Conclusion: The increased sICAM-1 was inversely associated with the decreased C₂ and the cardiac function in dilated cardiomyopathy patients. Background: There is some evidence showing that both myocardium and the blood vessels are damaged in dilated cardiomyopathy. However, changes in arterial compliance, circulating cytokines and endothelial progenitor cells, and their correlations remain unknown.Methods: Sixty-five dilated cardiomyopathy patients (aged 50.5±13.9 years) and forty-nine healthy volunteers (aged 50.1±8.1 years) were studied. Both large artery compliance (C₁) and small artery compliance (C₂) were measured with the CVProfilor DO-2020. Levels of vascular endothelial growth factor-A (VEGF-A), Vascular endothelial growth factor receptor -2(VEGF-R₂) and stromal cell-derived factol(SDF-1) were measured by enzyme-linked immunosorbent assays. Circulating endothelial progenitor cells were assessed by EPC colony-forming assays and flow cytometry (CD133⁺/CD34⁺ cells). Phagocytized DiI-acLDL and binded FITC-UEA-I were used to analyze endothelial lineage marker expression by immunofluorescence.Results: Although C₂ was markedly lower in DCM patients than in the control group (3.8±1.8 ml/mmHg×100 vs 5.0±2.2 ml/mmHgx 100, P<0.0001), there was no difference in C\ between the two groups (P > 0.05). Levels of VEGF-A and SDF-1 were markedly higher in DCM patients than in the control group (127.6±139.5 pg/ml vs 58.8±42.9 pg/ml, P < 0.0001; 457.7±281.2 pg/ml vs 236.4±86.1 pg/ml, P < 0.0001), there was also no difference in VEGF-R₂ between the two groups (P > 0.05). The number of colony-forming units (CFU) and the fraction of EPC were markedly higher in DCM patients than in healthy controls (23.5±12.8 vs 10.8±7.4 P<0.01; 2.5±1.5% vs 0.5±0.3% P<0.05). lgVEGF-A was positively correlated with both SDF-1 (r=0.658 P<0.001) and the numbers of EPC-CFU (r=0.435 P<0.05) in DCM patients. C₂ was inversely correlated with both lgVEGF-A (r=-0.543 P<0.001) and SDF-1 (r=-0.308 P<0.05) in DCM patients.Conclusions: Our study showed that a reduction in C₂ - small artery compliance, a sensitive marker reflecting endothelial dysfunction, was inversely correlated with an increase in circulating SDF-1 and VEGF-A. Circulating VEGF-A was positively correlated with a mobilization of EPC in DCM patients.