Adrenomedullin (AM) is a novel vasoactive peptide. The actions of AM include vasodilatation, reduction of arterial pressure, inhibition of vascular smooth muscle cell transference and proliferation, diuretic and natriuretic, inhibition of aldsterone secretion. Furthermore AM modulates extra cellular matrix deposition. So adrenomedullin plays an important role in the regulation of cardiovascular remodeling. This paper reviews the relationship between AM and cardiovascular remodeling.

AIM: To investigate the role of SMADs singal pathway in rat myocardial hypertrophy. METHODS: The rat model of myocardial hypertrophy was produced by constriction of the abdominal aorta. The wet left vertricular/body weight ratio (LVMI) was measured. The expression of TGF-beta l and Smad 2, 3, 7 mRNA were assessed by RT-PCR. RESULTS: The LVMI and the expression of TGF-beta l and Smad 2, 3, 7 mRNA in cardiomyothy were increased in 3 day after the operation and continued at last 4 weeks. The peak expression of TGF-beta l and Smad 2, 3, 7 mRNA was in 2 weeks after operation. The expression of Smad 7 was increased in 3 days after operation, but the peak was in 1 week after operation, then decreased. CONCLUSION: The signal protein Smad 2, 3, 7 are involved in the progress of rat myocardial hypertrophy produced by constriction of abdominal aorta. [

Aim To investigate the protective effects of MLT(melatonin) on acute ischemia-reperfusion induced myocardium damage in rats in vivo. Methods 36 anesthetized rats were separated randomly into 3 groups: ① Control group (n=12), without LAD (left anterior descending coronary artery) ligation and MLT; ② I/R(ischemia reperfusion) group(n=12), LAD was ligated for 10 min and reperfused for 15 min without MLT; ③ I/R+MLT group(n=12): MLT(10 mg?kg~(-1)) was in jected via peritonium 10 minutes before LAD ligation and reperfusion. ECG and haemodynamics were continuously monitored and recorded throughout the whole process, MDA(malondialdehyde, lipid peroxidation product, an index of myocardium damage) and SOD( superoxide dismutase ) activity were tested in the injuried myocardium. The hearts tissue of each group was also examinated by electron microscopy.Result The levels of MDA were significantly higher while the SOD activities were lower in I/R group compared with I/R+MLT and control group(P0.05). The haemodynamics indices of contractile and diastolic functions were also better in I/R+MLT group than inI/R group(P

Aim To explore the effects of lipoteichoic acid (LTA) induced delayed preconditioning (PC) on hypoxia-reoxygenation (H/R) injury of cultured human coronary artery endothelial cells (HCAECs), and to investigate the potential role of endogenous nitric oxide (NO) participated in the protective mechanism. Methods HCAECs were incubated for 2 h in a hypoxic atmosphere and reoxygenated for 4 h in a normoxic atmosphere. The delayed PC was induced by pretreatment with LTA assessed by the percentage of cellular injury with Trypan blue exclusion and by the amount of lactate dehydrogenase (LDH) in culture media. The NO level of the culture media was measured detect the expression of eNOS mRNA by RT-PCR method after cells were recovered from different points.Results LTA pretreatment significantly decreased the percentage of the killed cell and the concentration of LDH in media. Also, LTA pretreatment obviously raised the concentrations of NO in culture media. The protective effects of LTA were abrogated by pretreatment with N-monomethyl-L-arginine (L-NMMA).Moreover, the expression of eNOS mRNA was significantly upregulated after HCAECs exposure to LTA for 4 h following 2 h or 4 h recovery. Conclusion LTA could induce the delayed protection against H/R induced endothelial injury and dysfunction of cultured HCAECs. NO produced by eNOS acts initially as a trigger and subsequently as a mediator of delayed PC.

AIM: To study the potential effects of lipoteichoic acid (LTA)-induced delayed preconditioning (PC) on cardioplegic arrest/reperfusion injury in donor rat heart. METHODS: The rats were pretreated with LTA (1 mg/kg, ip) 24 h before the experiment, and the isolated hearts were subjected to arrested by cardioplegic solution and stored in Eurocollin's solution for 4 h by the Langendorff method, and to evaluate the changes of cardiac function at the reperfusion for 30 min and 60 min, to measure the amounts of MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and total nitric oxide (NO) oxidation products in the coronary effluent, and to detect myocardial apoptosis on tissue samples of left ventricle at the end of reperfusion by TUNEL staining. RESULTS: Pretreated with LTA significantly improved the recovery of cardiac function with a significant increase in coronary flow (CF), left ventricular developed pressure (LVDP), maximal rate of left ventricular developed pressure (+dp/dt_ max), and minimal rate of left ventricular decline pressure (-dp/dt_ max) at 30 min and 60 min of reperfusion (all P

BACKGROUND: Mesenchymal stem cells (MSCs) can differentiate into myocardial cells in vitro and in vivo, but the amount is small and directed differentiation rate is low.OBJECTIVE: To explore the effect of stem cell factor (SCF) on promotion of MSCs differentiating into myocardial cells.DESIGN: Opening experiment.SETTING: Institute of Cardiovascular Disease, Xianning College and Department of Cardiology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology.MATERIALS: The experiment was performed at the Experimental Center of Institute of Cardiovascular Disease, Xianning College from October 2003to August 2004. A total of 20 infant SD rats aged 1-2 days were selected for culture of myocardial cells. Another 25 clean adult SD rats were selected and randomly divided into SCF group, blank control group with 12 rats in each group. The left one rat was used for MSCs extraction, culture and purification.METHODS: ①MSCs were labeled with 4', 6-diamidino-2-phenylindole,dihydrochloride (DAPI) before co-culture. SCF was given into rats of the SCF group by subcutaneous injection successively for 5 days, 20 μg/kg per day. Isolated MSCs were co-cultured with myocardial cells that had been cultured for 3 days. Saline of the same volume was given in the blank control group by subcutaneous injection. MSCs without any intervention were co-cultured with myocardial cells that had been cultured for 3 days.②Expressions of MHC α/β and troponin T were recorded and measured with digital micro-camera shot and immunofluorescence technique, respectively. Percentage of DAPI labeled MSCs differentiating into myocardial cells was measured.MAIN OUTCOME MEASURES: ①Growth of MSCs, ②detection of labeling rate of DAPI on MSCs, ③analysis of activity and purity of co-cultured myocardial cells, and ④differentiation of MSCs into myocardial cells after co-culture.RESULTS: ①Bone marrow cell suspension was inoculated in plastic petri dish. Round cells scattered at the bottom of bottle. At hour 24 a few long fusiform shape adhered cells appeared following liquor change, and at day 4 many fusiform shape adhered cells appeared, which entered logarithm increased period. At days 8-12 80% were confluence. The proliferation of passage cells was more rapid. With liquor change and passage, the MSCs were purified gradually. ②Labeling rate of DAPI on MSCs was 100%. ③At 3-day in vitro culture of myocardial cells the percentage of beat cells was 63%, with beat frequency of 40-60 times per minute. Percentage of positive cells of troponin T expression was 75% examined with immunocytochemical technique. ④At co-cultured days 2 and 3, positive percentage of DAPI labeled MSCs expressing MHC α/β was significantly higher in the SCF group than in the blank control group (P ＜ 0.01). At the co-cultured days 3, 4 and 5, positive percentage of DAPI labeled MSCs expressing troponin T was obviously higher in the SCF group than in the blank control group (P ＜ 0.01).CONCLUSION: SCF has markedly accelerating effect on proliferation and differentiation of MSCs.

Objective To investigate the relationship of peroxisome proliferator activated receptor gamma ( PPAR?)C161T gene polymorphism with related diseases of metabolic syndrome. To disscuss the mechanism of the elderly diseases from gene level and the relation between the gene polymorphism and lipid metabolism. Methods Three hundred seventy one non-sibship subjects of Han nationality were investigated in this study, including 69 old healthy subjects, 302 elderly cases diagnosed as metabolic syndrome. PPAR? C161T gene polymorphism was determined by polymerase chain reaction and restriction fragment length polymorphism, and radioimmunoassay was used to detect serum insulin. The insulin resistance was obtained from homeostasis model assessment (HOMA), and blood glucose, blood lipoprotein, height, weight and so on were tested. The frequencies of PPAR? C161T genotypes and the allele were compared with the clinical data. Results (1) In the groups of old normal health and metabolic syndrome, "T" allele frequency was 0.217,0.201, and "C" allele frequency was 0.783, 0.798 . There was no significant difference between the groups. (2)The triglyceride in CC genotypes of the metabolic syndrome was significantly higher than that in "T" allele carriers. Conclusions (1) The distributing trend of PPAR ? C161T gene polymorphism of the Han nationality in Wuhan in the elderly normal healthy group was in accord with that in the group of the elderly metabolic syndrome. (2) PPAR ? C161T substitution can influence metabolic syndrome, especially in liporprotain metabolism. "T" allele is associated with lower level of triglyceride.

AIM: To investigate the effects of TGF-?_1 and signal protein Smad3 on rat cardiac myocyte hypertrophy.METHODS: The total protein was analyzed by flow cytometry and the ANF mRNA expression was measured by RT-PCR to judge the hypertrophy of cultured neonatal cardiac myocytes.Smad3 mRNA expression in cardiac myocytes was measured by RT-PCR,and the protein expression of Smad3 was analyzed by Western blotting.RESULTS: TGF-?_1 significantly increased the total protein in cardiac myocytes and promoted ANF mRNA expression,compared with control group.In cultured neonatal myocytes,AS-ODN of Smad3 inhibited myocyte hypertrophy induced by TGF-?_1.Smad3 mRNA and protein expression increased at 15 min after incubated with TGF-?_1,reached the peak at 1 h,and declined at 4 h.CONCLUSION: TGF-?_1 and signal protein Smad3 may participate in the progress of rat cardiac myocyte hypertrophy.

AIM:To investigate the effect of pretreatment of stem cell factor(SCF) and granulocyte colony-stimulating factor(G-CSF) on the proliferation and the differentiation of mesenchymal stem cells(MSCs) into cardiomyogenic cells.METHODS:The MSCs,isolated primarily from bone marrow,and purified by passage culture,were obtained from the adult rats of four groups:the rats were pretreated by 5 daily injections of SCF;the rats were pretreated with G-CSF;the rats were pretreated with SCF and G-CSF;the rats were treated without any intervention.The 4th passage of MSCs was labeled by DAPI and cellular cycle analysis was conducted by flow cytometry before co-culture.The neonatal rat cardiomyocytes cultured for 3 days were co-cultured with DAPI-MSCs.The percentage of the differentiation of MSCs into cardiomyogenic cells during the five co-culture days was analyzed.The morphologic changes of MSCs and the proteins expression of cardiac myosin heavy chain(MHC) and troponin T(TnT) were recorded respectively with digital microscope camera system and immunofluorescence technique.The percentage of the differentiation of MSCs into cardiomyogenic cells was also calculated.RESULTS:The percentage of MSCs in G0/G1 phase in SCF/G-CSF group was significantly lower than that in SCF group,G-CSF group and the control group.The percentage of MHC protein-positive MSCs in SCF/G-CSF group was markedly higher than that in SCF group,G-CSF group and the control group,and that in SCF group and G-CSF group was significantly higher than control group.The percentage of TnT protein-positive MSCs in SCF/G-CSF group,SCF group and G-CSF group was significantly higher than that in control group.CONCLUSION:SCF and G-CSF show the ability to stimulate the proliferation of MSCs and induce MSCs to differentiate into cardiomyocytes.The combination of using SCF and G-CSF is more effective than using only SCF or G-CSF.

AIM: To observe the effect of hemin on the expression of heme oxygenase-1(HO-1) in rat vascular smooth muscle cells(VSMCs). METHODS: Wistar rat aortic VSMCs were cultured in vitro and induced to proliferate by angiotensinⅡ(AngⅡ),hemin(a substrate and inducer of HO-1) and zinc protoporphyrin-Ⅸ(ZnPP,an inhibitor of HO-1)were added to induce and inhibit the expression of HO-1,respectively.The expression of HO-1 mRNA and protein were detected using reverse transcription polymerase chain reaction (RT-PCR)and Western blot,respectively. The relative amount of CO released into the media was quantitated as carbon monoxide hemoglobin(COHb)by enzyme-linked immunosorbent assay(ELISA),the proliferation of VSMCs was detected by MTT. RESULTS: The expression of HO-1 mRNA and protein in VSMCs and the amount of COHb in the media were increased significantly by hemin.Meanwhile the proliferation of VSMCs was suppressed markedly. CONCLUSION: The change of HO-1 mRNA and protein expression is the molecular base of the antiproliferation of endogenous CO .The HO-CO system might play a significant role in the development of cardiovascular diseases characterized by proliferation of VSMCs.