OBJECTIVE: To explore the effect of simvastatin on myocardiac fibrosis in patients with essential hypertension (EH). METHODS: Sixty EH patients were randomly assigned into 2 groups: Benazepril (10 mg/d) group (n = 28) and simvastatin (20 mg/d) + benazepril (10 mg/d) group. Procollagen type III aminoterminal peptide (PIIIP), and procollagen type IV aminoterminal peptide (PIVP) levels in serum as well as transforming growth factor beta 1 (TGFbeta1) level in plasma were measured by radioimmunoassay (RIA) before and 6 months after the treatment. Doppler ultrasound recordings were obtained from all patients before and 6 months after the treatment to determine several parameters related to the left ventricular anatomy and function. RESULTS: After 6 month of treatment, the mean blood pressure (MBP), PIIIP, PIVP, TGFbeta1, left ventricular mass index (LVMI), interventricular spectum dimension (IVSD), and left ventricular posterio wall dimension (LPWD) in the 2 groups were significantly lower than those before the treatment. TGFbeta1 decreased in the simvastatin and benazepril group compared with the benazepril group (P < 0.01). The ratio of early diastolic blood flow velocity of mitral valve (VE) and blood flow velocity of atrium systolic period (VA) in the 2 groups significantly increased after 6 months of treatment, and the ratio in the simvastatin and benazepril group was significantly higher than that in the enazepril group (P < 0.05). CONCLUSION Angiotension converting enzyme inhibitor combined with simvastatin is helpful to reduce the myocardial fibrosis and to improve the left ventricular hypertrophy and diastolic function in EH patients.
Adult ; Aged ; Aged, 80 and over ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Antihypertensive Agents ; therapeutic use ; Benzazepines ; therapeutic use ; Drug Therapy, Combination ; Female ; Fibrosis ; etiology ; prevention & control ; Humans ; Hypertension ; complications ; drug therapy ; Male ; Middle Aged ; Myocardium ; pathology ; Simvastatin ; therapeutic use

OBJECTIVE: To investigate the application of pulsed-wave Doppler tissue imaging ( PW-DTI) in evaluating left ventricular systolic and diastolic function in patients with chronic heart failure (CHF). METHODS: Mitral annular velocities (MAV) were measured by PW-DTI in 35 patients with CHF and 25 healthy subjects. Traditional indices for evaluating the global left ventricular function by conventional echocardiography were also studied as a comparison. RESULTS: Peak systolic, peak early diastolic, peak late diastolic mitral annular velocities ( Sa, Ea, Aa), and Ea/Aa ratio progressively decreased in CHF patients compared with the healthy subjects (P <0.01 ). Sa of the mitral annulus correlated linearly with the left ventricle ejection fraction (LVEF) (r =0.890, P < 0.01). Compared with the healthy subjects, Ea in all 3 subgroups of diastolic dysfunction in the CHF group significantly decreased (P <0.01). Aa in 2 subgroups (pseudonormal filling and restrictive filling) decreased (P < 0.01 ) and the decreased Ea/Aa was found in the delayed relaxation and pseudonormal filling subgroups compared with the healthy subjects (P<0.001). CONCLUSION MAV measured by PW-DTI can be used for assessing the left ventricular systolic and diastolic function in CHF patients.
Diastole ; Echocardiography, Doppler, Pulsed ; Female ; Heart Failure ; diagnostic imaging ; physiopathology ; Humans ; Male ; Systole ; Ventricular Function, Left ; physiology

OBJECTIVE: To investigate the myocardial fibrotic indices in patients with ischemic cardiomyopathy (ICM), and explore the mechanism of myocardial fibrosis. METHODS: The concentration of serum procollagen type III aminoterminal peptide (P III P), procollagen type IV aminoterminal peptide (P IV P), lamnin (LN), and hyaluronic acid (HA), as well as plasma angiotension II (AngII), aldosterone (ALD), and transforming growth factor beta 1 (TGFbeta1) in 46 ICM patients and 37 normal controls were measured by radioimmunoassay (RIA). The correlations between the plasma levels of AngII, ADL, TGFbeta1, and serum levels of P III P, P IV P, LN, and HA were analyzed. RESULTS: Compared with normal controls, the concentrations of serum P III P, P IV P, LN, HA, and plasma AngII, ADL, and TGfbeta1, significantly increased in ICM patients. AngII, ALD, and TGFbeta1 levels were positively correlated with the indices of myocardial fibrosis. CONCLUSION The myocardial fibrosis exists in ICM patients and the serum concentrations of P III P, P IV P, LN, and HA may be an indirect index of myocardial fibrosis. AngII, ADL, and TGFbeta1 levels play important roles in myocardial fibrosis.
Aged ; Cardiomyopathies ; pathology ; Collagen Type III ; blood ; Coronary Artery Disease ; pathology ; Female ; Fibrosis ; pathology ; Humans ; Hyaluronic Acid ; blood ; Laminin ; blood ; Male ; Middle Aged ; Myocardium ; pathology

OBJECTIVE: To analyze the echocardiographic abnormalities and the prevalence of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients and to evaluate the relationship between aCL and cardiac valvular abnormalities in SLE patients. METHODS: Ninety SLE patients were performed M-mode, 2-dimensional and Doppler echocardiography and aCL IgG and IgM were measured by an enzyme-linked immunosorbent assay (ELISA). According to the abnormalities in the echocardiography, the patients were assigned into valvular abnormality group and non-valvular abnormality group. Chi-square method was used to compare the difference of aCL prevalence between the two groups. RESULTS: The prevalence of echocardiographic abnormalities was 53.33%, and valvular abnormality (38.89%) and pericardial effusion (34.44%) presented most frequently. The aCL prevalence was 32.56% in the 43 SLE patients. The prevalence of aCL in the valvular abnormality group was significantly higher than that in non-valvular abnormality group (52.94% vs 19.23%, P<0.05). CONCLUSION The incidence of echocardiographic abnormalities is high in SLE patients, most often in valves and pericardium. The aCL is probably related to valvular damage in SLE patients.
Adolescent ; Adult ; Antibodies, Anticardiolipin ; blood ; Echocardiography, Doppler ; Female ; Heart Valve Diseases ; etiology ; immunology ; physiopathology ; Humans ; Lupus Erythematosus, Systemic ; complications ; immunology ; physiopathology ; Male

OBJECTIVE: To determine the diagnostic value of the integrated backscatter (IBS) technique for carotid artery atherosclerosis (AS), to investigate the correlation between IBS of carotid artery and the serum level of matrix metalloprotease-9(MMP-9), and to explore the effect of simvastatin on the IBS value of the carotid artery and serum MMP-9 level in hyperlipemia patients. METHODS: Fifty-eight patients with hyperlipemia and 26 normal controls were enrolled in this study. Patients with hyperlipemia were randomly divided into 2 groups: a simvastatin treatment group (20 mg/d) and a control group (without simvastatin treatment). Twenty-six healthy people were served as normal control group(n=26).The corrected IBS values(C-IBS) in carotid arteries,the intima-media thickness (IMT), and the serum MMP-9 levels were measured in the normal control group and the patients with hyperlipemia before and 8 weeks after the simvastatin therapy. RESULTS: The C-IBS of the simvastatin treatment group and the control group was significantly lower than that in the normal control group (all P<0.05). The IMT and MMP-9 in the simvastatin treatment group and the control group were significantly higher than those in the normal control group (all P<0.05). There was a negative correlation between the C-IBS of carotid arteries and the serum MMP-9 levels in the patients with hyperlipemia (r=-0.76,P<0.05). Eight weeks after the simvastatin treatment, the serum MMP-9 levels decreased significantly(P<0.05). CONCLUSION There is a negative correlation between the decreased C-IBS of carotid arteries and the increased serum MMP-9 levels in patients with hyperlipemia.The decreased C-IBS of carotid arteries and the increased serum MMP-9 levels may be the early indicators of atherosclerosis in hyperlipemia patients. The anti-atherosclerosis effect of simvastatin may partly attribute to its ability to lower the serum MMP-9.
Adult ; Anticholesteremic Agents ; therapeutic use ; Carotid Arteries ; diagnostic imaging ; drug effects ; Female ; Humans ; Hyperlipidemias ; blood ; diagnostic imaging ; drug therapy ; Male ; Matrix Metalloproteinase 9 ; blood ; Middle Aged ; Simvastatin ; therapeutic use ; Tunica Intima ; diagnostic imaging ; drug effects ; Tunica Media ; diagnostic imaging ; drug effects ; Ultrasonography

OBJECTIVE: To explore the association of metabolic syndrome(MS) with serum interleukin-10 (IL-10) and high sensitive C reactive protein(hs-CRP) in old men with MS. METHODS: Seventy patients with MS and 30 age-matched controls were enrolled. Blood pressure, waist circumference(WC), weight, height, body mass index(BMI), lipid-profile, fasting plasma glucose(FPG), fasting plasma insulin (FINS), homeostasis model assessment of insulin resistance(HOMA-IR),the serum IL-10, and hs-CRP levels were measured. The concentration of serum IL-10 was measured by enzyme linked immunosorbent assay (ELISA), and serum hs-CRP level by the latex-enhanced immuno- turbidimetric assay. RESULTS: Compared with the control group, the serum IL-10 level in the MS group was significantly lower (P<0.05), and the concentration of hs-CRP was obviously higher (P<0.05). Using Pearson's correlation analysis, the serum IL-10 level was negatively related with HOMA-IR(r=-0.684,P=0.000)and FINS(r=-0.742,P=0.000); hs-CRP was positively related with BMI(r=0.372,P=0.002), HOMA-IR(r=0.276,P=0.021)and FINS(r=0.312,P=0.008)in the MS group. Stepwise regression analysis suggested that FINS might be the influencing factors of IL-10; BMI and FINS might be the influencing factors of hs-CRP in patients with MS. CONCLUSION In old male patients with MS, the concentration of serum IL-10 decreases, and the serum hs-CRP level increases obviously. This suggests chronic inflammation.
Aged ; C-Reactive Protein ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Humans ; Inflammation ; complications ; Interleukin-10 ; blood ; Male ; Metabolic Syndrome ; blood ; complications ; Middle Aged

OBJECTIVETo observe the protective effect of metformin on the endothelial function and the mechanisms in rats with low-density lipoprotein (LDL) injection.

METHODSA single dose (4 mg/kg) of natural LDL was injected through the sublingual vein of rats to induce vascular endothelial dysfunction. Blood samples were then collected from the rats to detect the concentrations of malondialdehyde (MDA) and nitric oxide (NO), activity of superoxide dismutase (SOD) and serum lipid levels. The thoracic aorta of rats was obtained to assay acetylcholine (ACh)-induced endothelium-dependent relaxation (EDR) and sodium nitroprusside (SNP)-induced endothelium-independent relaxation. The effects of metformin pretreatment on the endothelial functions in the rats were investigated.

RESULTSA single-dose LDL significantly inhibited ACh-induced EDR without affecting SNP-induced endothelial-independent relaxation. The injection decreased serum NO and elevated serum MDA level, but had no effect on serum lipid level. Metformin markedly attenuated LDL-induced inhibition of EDR, serum MDA elevation, and serum NO reduction without affecting the serum lipid levels.

CONCLUSIONMetformin provides protection against vascular endothelial dysfunction induced by LDL in rats, the mechanism of which is probably associated with protection of endothelium-dependent relaxation factor and inhibition of the oxidative stress.

Animals ; Endothelium, Vascular ; drug effects ; physiopathology ; Endothelium-Dependent Relaxing Factors ; metabolism ; Lipoproteins, LDL ; administration & dosage ; Male ; Malondialdehyde ; blood ; Metformin ; pharmacology ; Nitric Oxide ; blood ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Vasodilation ; drug effects ; physiology

OBJECTIVETo investigate the protective effect of neferine against damages of endothelial cells induced by lysophos-phatidylcholine (LPC) and the relationship with asymmetric dimethylarginine (ADMA).

METHODThe human umbilical vein endothelial cells (HUVEC-12) were treated with LPC (10 mg x L(-1)) for 24 h to establish the model of endothelial cells damages; HUVECs were prior exposed to neferine (0.1, 1.0 or 10.0 micromol x L(-1) ) for 1 h, and then exposed to LPC in the presence of the neferine for 24 h. At the end of the experiment, the cultured medium was collected for measuring the concentration of nitric oxide (NO), aleic dialdehyde (MDA) as well as ADMA and the cells were collected for measuring the level of intracellular reactive oxygen species (ROS).

RESULTCompared with control group, exposure of endothelial cells to LPC (10 mg x L(-1)) for 24 h significantly increased the concentration of MDA and ADMA in the medium and the level of intracellular ROS and coinstantaneously significantly decreased the concentration of NO in the medium. Neferine (0.1, 1.0 or 10.0 micromol x L(-1)) significantly inhibited the elevated concentration of MDA, ADMA as well as the level of intracellular ROS and coinstantaneously significantly attenuated the decreased level of NO induced by LPC.

CONCLUSIONNeferine can protect the endothelial cells against damages induced by LPC and the protective effect is related to the decrease of the concentration of ADMA.

Arginine ; analogs & derivatives ; metabolism ; Benzylisoquinolines ; pharmacology ; Cell Line ; Endothelial Cells ; drug effects ; metabolism ; Humans ; Lysophosphatidylcholines ; pharmacology ; Malondialdehyde ; metabolism ; Nitric Oxide ; metabolism ; Reactive Oxygen Species ; metabolism

Liver cancer is one of the most common neoplastic diseases with high mortality in China. Currently, antimicrotubule drugs such as paclitaxel (PTX) and vincristine (VCR), are used as the common agents in the clinical chemotherapy for liver cancer. However, the responses of patients to these drugs vary markedly. Successful identification of intracellular factors influencing liver cancer's sensitivity to antimicrotubule drugs would be of great clinical importance. In this study, by engineering human hepatoma cell HepG2 to overexpress synuclein-gamma (SNCG), we investigated if SNCG is a molecular factor associated with the sensitivity to antimicrotubule drug treatment. Real-time RT-PCR and Western blotting assays showed SNCG was successfully overexpressed in HepG2/ SNCG cells compared with HepG2/Neo cells. The overexpressed SNCG altered the proliferation activity in HepG2 cells, which was 66% higher than that of HepG2/Neo cells through MTT method. The overexpressed SNCG also reduced sensitivity of HepG2 cells to antimicrotubule drugs: after PTX or VCR treatment, the proportion of HepG2/SNCG cells in G2/M arrest was significantly lower than that in HepG2/Neo cells. Correspondingly, HepG2/SNCG cells showed significantly lower mitotic index than HepG2/Neo cells. Meanwhile, HepG2/SNCG cells showed higher resistance to PTX and VCR than HepG2/Neo cells, with resistance index 21 and 15 respectively. Our studies suggested that the overexpression of SNCG could confer resistance to antimicrotubule drugs in hepatoma cells; and it indicated that SNCG may be as a potential response marker for antimicrotubule drugs in liver cancer chemotherapy.
Antineoplastic Agents, Phytogenic ; pharmacology ; Cell Cycle ; Cell Proliferation ; Drug Resistance, Neoplasm ; Gene Expression Regulation, Neoplastic ; Genetic Vectors ; Hep G2 Cells ; drug effects ; metabolism ; Humans ; Microtubules ; drug effects ; Mitosis ; drug effects ; Mitotic Index ; Paclitaxel ; pharmacology ; Plasmids ; RNA, Messenger ; metabolism ; Transfection ; Vincristine ; pharmacology ; gamma-Synuclein ; biosynthesis ; genetics ; physiology

Objective To investigate the mechanism and protective effect of Humanin(HN)on rotenone(Rot)-induced toxic damage for dopamine neurons.Methods The Rot-poisened PC12 cell model was constructed,and the control group,the Rot poisening group,the HN pretreated Rot poisening group,and the HN treatment group were set up.ELISA was used to detect the content of HN inside and outside of Rot-infected cells,CCK-8 assay was used to detect cell viability,and ATP detection kit was used to detect the intracellular ATP content.Dichloro-dihydro-fluorescein diacetate(DCFH-DA)assay was used to detect the level of reactive oxygen species(ROS)in cells.Western blotting was performed to detect the expression level of mitochondrial autophagy regulatory proteins Pink1,Parkin,p62,LC3,mitochondrial biogenesis regulatory protein PGC1α,division/fusion regulatory proteins OPA1,MFN2,DRP1,p-DRP1 and antioxidant stress regulatory proteins Keap1 and Nrf2.HBAD-mcherry-EGFP-LC3 adenovirus transfected cells was used to observed the number of autophagosomes and autophagolysosomes.Results The results showed that the intracellular concentration of HN in PC12 in the Rot poisening group was significantly higher than that in the control group(P＜0.05);Compared with the control group,the Rot poisening group had significantly decreased activity of PC12 cells,decreased ATP content and increased production of ROS.After the poisen of Rot in PC12 cells,the expression of Pink1 and p-Parkin,the ratio of LC3Ⅱ/LC3Ⅰ and the expression of p-DRP1 in mitochondrial fusion protein was increased,while the expression of p62,the expression of mitochondrial biogenesis protein PGC1 α,mitochondrial fusion proteins MFN2 and OPA1,and antioxidant stress proteins Keap1 and Nrf2 were decreased(all P＜0.05).The number of autophagosomes and autophagolysosomes in PC12 cells in the Rot poisening group was higher than that in the control group(P＜0.05),and HN pretreatment(20 μmol/L)could significantly improve the changes mentioned above caused by Rot poisening(P＜0.05).Conclusion HN ameliorates Rot-induced toxic damage for dopamine neurons by inhibiting mitophagy and mitochondrial division and promoting mitochondrial biogenesis and fusion,and anti-oxidative stress.