Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/ß-catenin signaling.

Hyperlipidemia has been shown to stimulate vascular smooth muscle cell (VSMC) proliferation. Wnt signaling pathway plays a critical role in embryonic development and cell proliferation. In this study, Sprague-Dawley rats fed with high-fat or normal diet for 12 weeks were sacrificed, and the thoracic aorta was harvested to determine wnt3a, ß-catenin, T-cell factor 4 (TCF4), and cyclin D1 expressions. VSMC proliferation within thoracic aorta and lipid accumulation within VSMCs were detected. Rat aortic VSMCs were cultured in serum from rats with hyperlipidemia or DKK-1; Wnt3a, ß-catenin, TCF4, and cyclin D1 expressions, and cell cycle distribution were determined. The findings demonstrated that increased number of VSMCs, lipid droplets, and vacuoles within thoracic aorta in the high-fat-fed group. Compared with controls, VSMCs from high-fat-fed rats showed higher mRNA expressions of wnt3a, ß-catenin, TCF4, and cyclin D1, as well as in VSMCs cultured with hyperlipidemic serum. After 24 h, VSMCs stimulated with hyperlipidemic serum showed significantly increased cell number and S-phase entry compared with cells exposed to normolipidemic serum. These effects were blocked by DKK-1. These results suggest that Wnt/ß-catenin signaling plays an important role in hyperlipidemia-induced VSMC proliferation.

[Effect of Astragalus on cytokines in patients undergoing heart valve replacement].

OBJECTIVE: To evaluate the effect of astragalus (As) on cytokines in patients undergoing heart valve replacement (HVR). METHODS: Thirty patients undergoing HVR were randomized into the As group and the control group. Cardiopulmonary bypass (CPB) was set up routinely and to the As group, As injection (40 mL, 10 mL containing 2 g of crude drug) was added into the prime solution just before CPB. Blood samples were collected at different time points during and after CPB for cytokines determination, including tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), IL-8 and IL-10 by ELISA. RESULTS: All the indexes measured were insignificantly different between groups before skin incision, they began to increase by the end of CPB (P < 0.05), reached the peak 3 h after CPB and then decreased gradually, TNF-alpha returned to the baseline level 24 h after operation. Meanwhile, levels of IL-6, IL-8 and IL-10 decreased obviously but still above the baseline. Comparisons between groups at different time points showed that levels of IL-6 were not different significantly (P > 0.05), those of IL-10 were higher at all time points, and TNF-alpha and IL-8 at 3 h, 6 h and 12 h after CPB were significantly lower in the As group (all P < 0.05). CONCLUSION: Astragalus may decrease the inflammation cytokine promoting factors, and increase the level of anti-inflammatory cytokine (IL-10), so it could attenuate the inflammation reaction in patients after HVR.

A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese.

OBJECTIVES: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study, we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. DESIGN AND METHODS: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphism in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. RESULTS: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI=1.1-2.9, P<0.0001) and 1.9 (95% CI=1.3-3.2, P<0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. CONCLUSIONS: The present findings suggest that the C allele at nucleotide -778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese.

[Analysis of the risk factors of acute renal insufficiency following coronary artery bypass grafting].

OBJECTIVE: To study the risk factors of acute renal insufficiency (ARI) following coronary artery bypass grafting (CABG). METHODS: The clinic data of 2242 patients undertaking CABG between July 1997 and July 2006 were retrospectively analyzed, and ARI following CABG was included. RESULTS: ARI occurred in 219 patients, with an incidence of 9.8%. Univariate analysis revealed that advanced age, diabetes mellitus, preoperative chronic renal dysfunction, left main disease, low left ventricular erection faction, emergency operation, on-pump CABG, ascending aortic atherosclerosis, postoperative respiratory function insufficiency and low cardiac output syndrome were significantly related to ARI following CABG, and logistic multivariate regression analysis showed that presence of advanced age (P = 0.031), preoperatively chronic renal dysfunction (CrCl or= 150 micromol/L, P = 0.041), on-pump CABG (P < 0.001), postoperative respiratory function insufficiency (P = 0.013) and low cardiac output syndrome (P = 0.004) were independent risk factors of ARI. CONCLUSIONS: Advanced age, preoperatively chronic renal dysfunction, on-pump CABG, postoperative respiratory function insufficiency and low cardiac output syndrome are the risk factors of ARI following CABG.

Significance of changes in transforming growth factor-beta mRNA levels in autogenous vein grafts.

BACKGROUND: This study was designed to investigate changes in mRNA levels of transforming growth factor-beta (TGF-beta), collagen I, and collagen III in autogenous vein grafts. METHODS: Twenty-four New Zealand rabbits were randomly divided into 4 groups with 6 rabbits each. The external jugular veins of the New Zealand rabbits were harvested and grafted into the ipsilateral carotid artery. All rabbits were fed with a standard diet. After the operation, the rabbits were sacrificed at 1, 2, 3, or 4 weeks. TGF-beta, collagen I, and collagen III mRNA levels in the venous grafts were measured by semiquantitative methods at every time point. The contralateral external jugular veins were also harvested and analyzed as controls. Glyceraldehyde-3-phosphate dehydrogenase was used as an internal standard to normalize all samples for potential variations in mRNA content. In order to observe the expression of TGF-beta protein, immunohistochemical SABC methods were used. RESULTS: One week postoperation, the mRNA level of TGF-beta was upregulated to 1.73 +/- 0.19 in the vein graft and 1.21 +/- 0.16 in the control vein (P < 0.01). High mRNA levels were maintained until week 4 postoperation. The mRNA levels of collagen I and collagen III were also significantly increased to 2.18 +/- 0.21 versus 1.12 +/- 0.24 and 1.08 +/- 0.13 versus 0.83 +/- 0.12, respectively (P < 0.05). Immunohistochemical staining revealed a higher density of TGF-beta expression in the vein grafts. CONCLUSIONS: An uninterrupted increase in mRNA levels of TGF-beta, collagen I, and collagen III is observed in autogenous vein grafts. This increase may be the major cause of intimal hyperplasia, sclerosis, and even graft failure.

Cardiac myxoma and myxosarcoma: clinical experience and immunohistochemistry.

From January 1978 to February 1999, 120 patients (42 males and 78 females) with cardiac myxoma (115) or myxosarcoma (5) underwent surgical excision or biopsy. There were 5 early postoperative deaths (mortality, 4.2%). Seventy-three survivors were followed up for 0.75 to 20.25 years (mean, 9.42 years); they comprised 4 myxosarcoma patients who all had recurrence or metastasis, and 69 myxoma patients who had no evidence of recurrence or metastasis. Neither familial myxoma nor Carney complex was found. The 5 cases of myxosarcoma and 18 randomly selected cases of myxoma were evaluated for proliferative activity, metastatic potential, and oncogene products by immunohistochemistry. The expression of p53 and Bcl-2 was similar in both groups. Overexpression of proliferating cell nuclear antigen and low expression of nm23 in myxosarcoma are consistent with the high rate of recurrence and metastasis of this tumor. Surgical resection of sporadic myxoma is a safe and effective treatment with satisfactory early and long-term results. However, the prognosis of myxosarcoma is still disappointing. Regular echocardiography and chest radiography or computed tomography are necessary for early detection of recurrence or metastasis of myxosarcoma.

[Establishment of model human stem cell of transplantation into myocardium of chick embryos].

OBJECTIVE: To establish an animal model of human stem cell transplantation into myocardium in chick embryos. METHODS: Hoechsst 33,258 labeled human primordial germ cells (hPGC) were microsurgically injected into the myocardium of 633 chick embryos of 3-4 days development. Ten days after, the hearts were isolated from the 94 surviving chick embryos, embedded, and sliced. In situ hybridization (ISH) with human specific DNA Alu probe was conducted on the sections with fluorescence to detect the existence of transplanted PGC. Immunohistochemistry with human-myocardium-specific antibody cTnT was conducted on the adjacent sections to observe the differentiation of human myocardial cells. RESULTS: ISH showed that PGC were detected in the myocardium of chick embryos 10 days post-operationally. Immunohistochemistry showed that the myocardium added with antibody in adjacent sections was cTnT-positive and the myocardium untreated with antibody was cTNT-negative. Successful cell transplantation occurred in 15.3% +/- 2.4% of chick embryos. CONCLUSION: Establishment of an animal model of cell transplantation of human stem cells into myocardium in chick embryos is feasible.

[Off-pump coronary artery bypass grafting in patients over the age of seventy].

OBJECTIVE: To discuss the choice of surgical methods and the safety and efficacy of off-pump coronary artery bypass grafting (OPCAB) in elderly patients. METHODS: From Sept. 1997 to Feb. 2003, 63 cases over the age of seventy (including seventy) undertook OPCAB in our department. We compared the clinical data of those patients with that of 94 cases undertook conventional coronary artery bypass grafting (CABG) at the same age group and that of 58 cases younger than seventy received OPCAB. RESULTS: The clinical outcomes of OPCAB is better than that of CABG in elderly patients concerning inotropic drug, postoperative transfusion, re-operation, intubation time, complications incidence and in-hospital mortality. Furthermore, there is no significant difference of complication incidence and in-hospital mortality between the elderly OPCAB group and the younger OPCAB group. CONCLUSIONS: OPCAB is a safe and efficacious method of myocardial revascularization in the elderly.

Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in cardiomyocytes independent of endothelial cells.

INTRODUCTION: Vasostatin-1 (VS-1) has been suggested in protecting hypoxia/reoxygenation (H/R) injuries in isolated hearts. However, the molecular mechanisms remained to be elucidated. METHODS: Cardiomyocytes were treated with recombinant Ad-VS-1 adenoviral vector before H/R. Cell viability was studied using MTT methods and annexin V-FITC flow cytometry. Intracellular oxidative stress was measured by superoxide dismutase (SOD) and malondialdehyde (MDA), and inflammatory reactions by enzyme-linked immunosorbent assay (ELISA). Measurement of myocardial nitrous oxide synthase (NOS) was determined by serum nitric oxide (NO) concentrations using nitrite reductase and endothelial nitric oxide synthase (eNOS) by Western blotting. Inhibitors of the NOS system, including hemoglobin and KT5823, were applied to verify the results. RESULTS: In comparison of the blank group, cardiac myocytes overexpressing VS-1 showed significant decrease in apoptosis, intracellular oxidative stress, and inflammatory reactions (P < 0.05). In addition, serum NO concentrations and expression of eNOS were notably enhanced (P < 0.05). These protective effects of VS-1 were suppressed in the presence of apoptosis-inducing agents. CONCLUSIONS: Overexpression of VS-1 in cardiomyocytes could limit the H/R injuries at molecular levels. The protective effects were independent of endothelial cell function, suggestive of a potential therapeutic target for patients with myocardial ischemia in the future.

Early outcomes of isolated coronary artery bypass grafting in Chinese aged patients with diabetes mellitus.

OBJECTIVE: To compare the early outcomes of coronary artery bypass grafting (CABG) in aged diabetic patients, and evaluate the affection of diabetes on the early outcomes of CABG in aged patients. METHODS: The study took place in the Department of Cardiovascular Surgery, Shanghai Jiao Tong University Affiliated First People's Hospital, Shanghai, China, between January 2000 and July 2008. Five hundred and ninety-three elderly patients (age > or = 70-years-old), undergoing isolated CABG were retrospectively divided into diabetic group and non-diabetic group. We analyzed the pre-operative, intra-operative, and post-operative variables of the 2 groups. The t-test, Chi-square test, and multivariate logistic regression were used to determine the differences between the 2 groups of patients. RESULTS: There was no statistical difference of pre-operative and intraoperative variables between the 2 groups, except that there were more left main coronary artery diseases in the diabetic group. Values in the post-operative period such as morbidity, complications, and blood infusion had no differences between the 2 groups. Diabetes mellitus and age are not the risk factors for in-hospital mortality. CONCLUSION: Coronary artery bypass grafting in elderly patients is plausible. Furthermore, diabetic patients could get the same surgical results as those non-diabetic patients.