Autologous mesenchymal stem cell implantation promotes myocardial expressions of growth factors and improves cardiac function in failing rat hearts / 中华心血管病杂志

<p><b>OBJECTIVE</b>To explore the underlying mechanism of mesenchymal stem cells (MSCs) transfer induced cardiac function improvement in failing hearts.</p><p><b>METHODS</b>Congestive heart failure (CHF) was induced in rats by cauterization of the heart wall. MSCs were cultured from autologous bone marrow and injected into the border zone and the remote myocardium 5 days after cauterization.</p><p><b>RESULTS</b>Ten weeks later, cardiomyocyte nucleus mitotic index, capillary density and expression of insulin-like growth factor 1 (IGF-1), hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) were significantly increased in the border zone and significantly reduced in the remote myocardium in CHF rats (all P<0.05 vs. sham). Besides cardiac function improvement and left ventricular remodeling attenuation evidenced by hemodynamic and echocardiographic examinations, expressions of IGF-1, HGF and VEGF in the remote myocardium and in the border zone were also significantly upregulated (P<0.05 or P<0.01 vs. CHF), and cardiomyocyte nucleus mitotic index as well as capillary density were significantly increased in CHF rats with MSCs (P<0.05 or P<0.01 vs. CHF). Moreover, collagen area was significantly reduced and myocardial area was significantly increased in the border zone in these rats too.</p><p><b>CONCLUSION</b>Autologous MSC implantation upregulated expressions of growth factors enhanced cardioangiogenesis which might be the underlying mechanisms for improved cardiac function and attenuated left ventricular remodeling induced by MSCs transplantation in failing rat myocardium.</p>

Effects of C-reactive protein on bone marrow-derived endothelial progenitor cell function / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effects of C reactive protein (CRP) on endothelial progenitor cell (EPCs) function.</p><p><b>METHODS</b>Mononuclear cells (MNCs), isolated from bone marrow by density gradient centrifugation combined with adherent cell filtration, were plated on fibronectin coated culture dishes. After 7 days, adherent cells were cultured with different concentrations of CRP (0, 5, 10, 15, 20 microg/ml) for 48 hours. EPCs proliferation and migration ability were observed and adhesion assay was performed. The eNOS mRNA expression of EPCs were measured by RT-PCR.</p><p><b>RESULTS</b>The number of EPCs in CRP groups (10, 15, 20microg/ml) was obviously lower than that in control group (54 +/- 3, 47 +/- 3, 39 +/- 5 vs.60 +/- 3, P < 0.01). EPCs proliferation capacity was inhibited in CRP groups (10, 15, 20 microg/ml) compared with that in control group (0.297 +/- 0.036, 0.273 +/- 0.013, 0.259 +/- 0.035 vs. 0.345 +/- 0.014, P < 0.01). EPCs migration capacity was inhibited significantly in CRP groups (5, 10, 15, 20 microg/ml) than that in control group (28 +/- 2, 22 +/- 3, 19 +/- 3, 16 +/- 2 vs. 30 +/- 2, P < 0.05). EPCs adhensive number was lower in CRP groups than that in control group (11 +/- 2, 9 +/- 2, 6 +/- 2, 5 +/- 1 vs. 12 +/- 2, P < 0.05). The mRNA expressions of eNOS in CRP groups were significantly lower in control group. And compared with control group, NOS activity decreased significantly in CRP groups (10, 15, 20 microg/ml) (57.44 +/- 3.25, 48.37 +/- 3.86, 36.82 +/- 4.89 vs. 68.56 +/- 2.82, P < 0.01).</p><p><b>CONCLUSION</b>CRP could both reduce EPCs number and inhibit EPCs functions.</p>

Sirolimus inhibits the differentiation, proliferation and migration of endothelial progenitor cells in vitro / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of sirolimus on differentiation, proliferation, adhesion and migration of endothelial progenitor cells (EPC) in vitro.</p><p><b>METHODS</b>(1) Mononuclear cells (MNC) were isolated from rat bone marrow by Ficoll density gradient centrifugation and cultured on fibronectin-coated culture dishes with or without sirolimus (0.01 - 100 ng/ml) for 12 days. (2) After 8 days cultured, attached cells were treated with sirolimus (0.1 - 200 ng/ml) or vehicle for various time points (12 h, 24 h, 48 h and 96 h). EPC were identified as adherent cells double positive stained for FITC-UEA-I and DiI-acLDL under laser confocal immunofluence microscope. EPC proliferation, migration were assayed with MTT assay and modified Boyden chamber assay respectively.</p><p><b>RESULTS</b>EPC number differentiated from MNC at 12 days was significantly lower in sirolimus treated cells in a dose-dependent manner than that of vehicle-treated cells. Sirolimus also significantly inhibited the proliferative, migratory and adhesive capacity of EPC in a time and dose dependent manner.</p><p><b>CONCLUSION</b>Present results suggested that sirolimus could inhibit EPC differentiation from MNC and reduce the proliferation, migration and adhesion capacities of EPC.</p>

Stromal Interaction molecule 1 STIM1 Knockdown Inhibits Proliferation of Vascular Smooth Muscle Cells / 中华高血压杂志

Objective To explore the role of stromal interaction molecule 1(STIMI)on prohteration and intra- cellular Ca~(2+)change in vascular smooth muscle ceils(VSMC).Methods Rat VSMC were isolated from SD rats and primary cultured.Ad-si/rSTIM1 and Ad-hSTIM1 were transfected into VSMC.The protein of STIM1 was measured by Western blot,the proliferation of VSMC was analyzed by ~3H-thymidine(~3H-TdR)incorporation and cell count,the intracellular Ca~(2+)change was assessed By Aquaeosmos system.Ruselts Fourty-eight hours after transfection,as compared with Ad-hSTIMI group,the Ad-si/rSTIMI VSMC had lower expression of STIM1 protein (P

The role of cyclooxygenase on angiogenesis and endothelial progenitor cell mobilization in rat ischemic myocardium / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of COX1 and COX2 on angiogenesis and endothelial progenitor cell mobilization in rats with experimental myocardial infarction (MI).</p><p><b>METHODS</b>The rats were randomly divided into 3 groups: MI group, MI plus rofecoxib group and MI plus valeryl salicylate group. At the 7th day after operation, circulating EPCs, plasma VEGF and HIF-1alpha mRNA of ischemic myocardium were measured. At the 28th day post operation, capillary densities were also measured in ischemic myocardium.</p><p><b>RESULT</b>Compared with the MI group and the MI plus valeryl salicylate group, circulating EPCs, plasma VEGF, HIF-1alpha mRNA and capillary densities of ischemic myocardium were all decreased in MI plus rofecoxib group.</p><p><b>CONCLUSION</b>The present study revealed that COX2 play an important role with angiogenesis and endothelial progenitor cell mobilization in rat with experimental MI by modulating expression of VEGF and HIF-1alpha.</p>