Coronary Artery Disease: Wu L

Lee PW, Zhang Q, Yip GW, Wu L, Lam YY, Wu EB, Yu CM. · Li Ka Shing Institute of Health and Sciences, Institute of Vascular Medicine, Division of Cardiology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China. · Clin Sci (Lond). · Pubmed #18684109 No free full text.

Abstract: The present study aims to evaluate LV (left ventricular) mechanical dyssynchrony in CAD (coronary artery disease) with preserved and depressed EF (ejection fraction). Echocardiography with TDI (tissue Doppler imaging) was performed in 311 consecutive CAD patients (94 had preserved EF > or =50% and 217 had depressed EF <50%) and 117 healthy subjects to determine LV systolic and diastolic dyssynchrony by measuring Ts-SD (S.D. of time to peak myocardial systolic velocity during the ejection period) and Te-SD (S.D. of time to peak myocardial early diastolic velocity during the filling period) respectively, using a six-basal/six-mid-segmental model. In CAD patients with preserved EF, both Ts-SD (32.2+/-17.3 compared with 17.7+/-8.6 ms; P<0.05) and Te-SD (26.2+/-13.6 compared with 20.3+/-8.1 ms; P<0.05) were significantly prolonged when compared with controls, although they were less prolonged than CAD patients with depressed EF (Ts-SD, 37.8+/-16.5 ms; and Te-SD, 36.0+/-23.9 ms; both P<0.005). Patients with preserved EF who had no prior MI (myocardial infarction) had Ts-SD (32.9+/-17.5 ms) and Te-SD (28.6+/-14.8 ms) prolonged to a similar extent (P=not significant) to those with prior MI (Ts-SD, 28.4+/-16.8 ms; and Te-SD, 25.5+/-15.0 ms). Patients with class III/IV angina or multi-vessel disease were associated with more severe mechanical dyssynchrony (P<0.05). Furthermore, the majority of patients with mechanical dyssynchrony had narrow QRS complexes in those with preserved EF. This is in contrast with patients with depressed EF in whom systolic and diastolic dyssynchrony were more commonly associated with wide QRS complexes. In conclusion, LV mechanical dyssynchrony is evident in CAD patients with preserved EF, although it was less prevalent than those with depressed EF. In addition, mechanical dyssynchrony occurred in CAD patients without prior MI and narrow QRS complexes.

Wu L, Xu DL, Deng LH, Ye TC, Deng H, Li Y. · Department of Cardiology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. · Nan Fang Yi Ke Da Xue Xue Bao. · Pubmed #18676273 links to  free full text

Abstract: OBJECTIVE: To analyze the patterns of serum soluble CD14 (sCD14) and C-reactive protein (CRP) alterations in patients with chronic heart failure (CHF) and investigate the correlations of sCD14 variation to the etiology, clinical symptoms, and the number of mononuclear cells in these patients. METHODS: This study involved 246 CHF patients stratified according to their etiology and clinical symptoms, with 107 normal individuals serving as the control group. Blood samples were collected from these patients the next day after admission and also from the control subjects for measuring serum sCD14 and CPR levels using enzyme-linked immunosorbent assay (ELISA) and rate nephelometry, respectively. RESULTS: The CHF patients had significantly higher serum levels of sCD14 and CRP than the control subjects (P<0.01). In the CHF patients, serum sCD14 and CRP levels differed significantly in the patients with clinical symptoms of different severities (F=3.787, P=0.024), and those with moderate and severe symptoms had significantly higher levels than the asymptomatic patients (P<0.05). The difference in etiologies also resulted in significant difference in sCD14 levels (P<0.05), which were significantly lower in coronary artery disease group than in hypertension group (P<0.05). Significant positive correlations were found between sCD14 and the CRP levels in the CHF patients (r=0.227, P=0.018) and between sCD14 level and the clinical symptoms (r=0.206, P=0.001), but sCD14 level was not correlated to the absolute or relative number of mononuclear cells. CONCLUSIONS: Serum sCD14 and CRP levels are significantly elevated in CHF patients, but this condition may vary as the etiologies and clinical symptoms differ. Increased mononuclear cells do not contribute to the elevation of serum sCD14.

Fang J, Wu L, Chen L. · Fujian Institute of Coronary Artery Disease, Union Hospital, Fujian Medical University, Fuzhou, PR China. · Acta Cardiol. · Pubmed #18664030 No free full text.

Abstract: OBJECTIVE: The effect of inhibiting mitochondrial permeability transition (MPT) on cardioprotection induced by ischaemic postconditioning remains debatable. The aim of the present study was to investigate whether ischaemic postconditioning attenuates cardiomyocyte ultrastructure injury and apoptosis by blocking MPT. METHODS AND RESULTS: Sprague-Dawley rats were randomly allocated to eight groups (n = 12) including sham without ischaemia (I), control given 30 min 1 and 5 min or 120 min reperfusion (R), postconditioning (Post) treated the same as control and 3 cycles of 10 s R and 10 s I before R, preconditioning (Pre) treated the same as control and 3 cycles of 5 min 1 and 5 min R before 30 min 1, and other groups treated the same as control or Post and given cyclosporin A (CsA) or atractyloside (Atr). Infarct size was evaluated by TTC, ultrastructure by electron microscope, MPT by spectrophotometry, and apoptosis by TUNEL. Compared with the control treatment, the Post, CsA and Pre treatments had smaller infarct size, less reduction in optical density at 540 nm (OD540) for MPT (20.2% +/- 2.3% versus 12.1% +/- 1.8%, 11.2% +/- 3.3% and 12.1% +/- 5.6%, P < 0.01, respectively), lower mitochondrial score (2.09 +/- 0.27 versus 1.27 +/- 0.27, 0.97 +/- 0.26 and 1.28 +/- 0.32, P < 0.01, respectively) and percentage of apoptosis (34.9% +/- 2.6% versus 17.5% +/- 1.7%, 17.6% +/- 2.1% and 17.2% +/- 2.1%, P < 0.01, respectively). Post-induced cardioprotection was abrogated by Atr and failed to be enhanced by CsA. CONCLUSIONS: Blockage of MPT may be involved in attenuation of ultrastructure injury and apoptosis by ischaemic postconditioning.

Zeng X, He H, Yang J, Yang X, Wu L, Yu J, Li L. · College of Life Sciences, Zhejiang University, Hangzhou, Zhejiang, PR China. · J Ethnopharmacol. · Pubmed #18579111 No free full text.

Abstract: AIM: Cardiac infarction is one of the main causes of death in both developing and developed countries over past decades. Currently available approaches for treating patients with this disease are not satisfactory. Traditional Chinese medicines have been increasingly paid attention to. The aim of this study was to characterize the dynamic protective effects of Guanxin No. 2 decoction (GX II) on cardiac dysfunction combined with the blood viscosity and myocardial hypertrophy parameters in myocardial infarction (MI) rats. METHODS: Male Sprague-Dawley rats (180-200 g) were randomly divided into three groups: sham-operated, coronary artery ligation (CAL), and CAL plus GX II (GX II, 10.0 g raw materials/kg/d, bid, p.o.). The experiment was carried out at 4 time points as the 3rd, 7th, 14th, and 28th day after ligation. RESULT: It was found that on the one hand, GX II could significantly improve the heart function, and remarkably decrease infarct size and inhibit ventricular remodeling. On the other hand, GX II showed some unique effects such as angiogenesis which was induced in the left ventricular tissue. This result was consistent with the finding of an augmented vascular endothelial growth factor (VEGF) expression in this area. CONCLUSIONS: The studies demonstrated that GX II exerted extensively beneficial cardioprotective effect on CAL rats, it might stimulate angiogenesis of ischemic region to compensate blood supply to the heart via upregulated VEGF expression.

Feng D, Li Q, Zhang K, Jiang X, Leng S, Deng H, Feng J, Sun T, Wu L, Zhou C. · Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. · J Huazhong Univ Sci Technolog Med Sci. · Pubmed #18480984 No free full text.

Abstract: To develop a more efficient antithrombotic way after coronary artery bypass grafting (CABG), the anticoagulant effects were compared of human tissue factor pathway inhibitor (TFPI) gene transfection and aspirin oral administration (traditional method) on vein grafts. An eukaryotic expression plasmid pCMV-(Kozak) TFPI was prepared. Animal model of carotid artery bypass grafting was constructed. In operation, endothelial cells of vein grafts in TFPI group and empty plasmid control group were transfected with pCMV-(Kozak) TFPI and empty plasmid pCMV respectively, while no transfection was conducted in aspirin control group. After operation, aspirin (2 mg.kg(-1).(-1)) was administered (i.g.) in aspirin control group. Three days later, grafts (n=10) were harvested for RT-PCR, Western blotting and immunohistochemical analyses of exogenous gene expression and for pathological, scanning electron microscopic observation of thrombus. Thirty days later, the patency rates of remnant grafts (n=10) were recorded by vessel Doppler ultrasonography. Human TFPI gene products were detected in gene transferred vein grafts. Three days later, thrombi were found in 7 animals of aspirin control group and in 8 animals of empty plasmid control group, but in only 1 of TFPI group (P<0.01). Thirty days later, 5 grafts were occluded in empty plasmid control group, but none of grafts was occluded in the other groups (P<0.05). The endothelial surfaces of grafts in both of the control groups were covered with aggregated erythrocytes and platelets, and it were not seen in TFPI group. It was suggested that the anticoagulant effects on vein grafts of human TFPI gene transfection are better than those of aspirin.

He H, Shi M, Zeng X, Yang J, Li Y, Wu L, Li L. · Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zijingang Campus, Zhejiang University, Hangzhou, China. · J Ethnopharmacol. · Pubmed #18439775 No free full text.

Abstract: AIM: To study the cardioprotective effect of salvianolic acid B (Sal B) on cardiac dysfunction. We hypothesized that hyperleptinemia may correlate with abnormal expression of sarco/endoplasmic reticulum ATPase 2a (SERCA2a), phospholamban (PLB) and endothelin-reactive oxygen species (ET-ROS) pathways in rats with large myocardial infarction (MI). METHODS: Large MI was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into four groups: sham, MI, MI+l-Sal B (50 mg/(kg d)), p.o. for 4 weeks), and MI+h-Sal B (100 mg/(kg d)), p.o. for 4 weeks). RESULTS: In MI rats, hemodynamic and echocardiographic abnormalities, cardiac remodeling, and histological changes with features of cardiac failure were associated with hyperleptinemia accompanied by oxidative stress and upregulated OB-Rb, ET pathway mRNA expression and downregulated SERCA2a and PLB mRNA and protein expressions in the myocardium. CONCLUSIONS: The studies demonstrated that an activated leptin pathway correlated with abnormal expression of SERCA2a, PLB and an activated ET-ROS system in the affected myocardium. Sal B exerts beneficial actions on cardiac function in rats with large MI, mainly suppressing upregulation of leptin and ET pathways and oxidative stress, and recovering the normal expressions of SERCA2a and PLB in myocardium.

He H, Yang X, Shi M, Zeng X, Yang J, Wu L, Li L. · Institute of Chinese Herb Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, P. R. China. · J Pharm Pharmacol. · Pubmed #18088512 No free full text.

Abstract: The present study was conducted to investigate whether hydroxysafflor yellow A (HSYA) has a protective effect on acute and chronic heart failure (AHF/CHF) induced by ligation of the left anterior descending coronary artery for 3 h and 8 weeks, respectively. The rats were divided into the following groups: sham operation, coronary artery ligation (CAL), CAL+HSYA (100 mg kg(-1) by gavage) and CAL+diltiazem (20 mg kg(-1) by gavage). In the AHF model, heart function, as determined by haemodynamic studies and echocardiography, was improved significantly by pretreatment with HSYA or diltiazem. Significant reductions in elevated serum creatine phosphokinase, lactate dehydrogenase, malondialdehyde (MDA), glutamic oxalacetic transaminase, glutamic pyruvic transaminase and blood viscosity were observed, and the activity of serum superoxide dismutase (SOD) was enhanced (all P<0.01). In the CHF model, HSYA and diltiazem restored abnormal heart function, and completely suppressed the elevated plasma atrial natriuretic polypeptide (ANP) and endothelin-1 (ET-1), serum and left-ventricular tissue inducible nitric oxide (NO) synthase (iNOS), NO and MDA, and improved the decrease in SOD. HSYA and diltiazem improved cardiac performance in AHF and reduced cardiac remodelling in CHF by reducing tissue weight indices: left ventricular weight/body weight (BW), right ventricular weight/BW, kidney weight/BW and lung weight/BW, and attenuating increases in infarct size, inner diameter of the left ventricle and collagen volume fraction in non-infarcted areas, and the decrease in mean wall thickness of infarcted myocardium. These results suggest that HSYA exerted beneficial actions in cardiac performance in models of both AHF and CHF, mainly by suppressing ET-1, iNOS and oxidative stress in infarcted tissue.

Wu L, Qiao H, Li Y, Li L. · College of Pharmaceutical Sciences, Zhejiang University, Zijingang Campus of Zhejiang University, Hangzhou 310058, China. · Phytomedicine. · Pubmed #17870452 No free full text.

Abstract: Ischemic heart diseases have been the leading cause of death in both developed and developing countries over the past decades. The aim of this study was to investigate the cardioprotective effects of the complex preparation (called Shenge), made of puerarin (isolated from Pueraria lobata Ohwi., also called Kudzu) and Danshensu (isolated from the Chinese herb, Salvia miltiorrhiza), on acute ischemic myocardial injury in rats and its underlying mechanisms. The left anterior descending (LAD) coronary artery was occluded to induce myocardial ischemia in the hearts of SD rats. Shenge was injected into the tail vein 15 min after occlusion at doses of 0, 30, 60, or 120 mg/kg body wt. ST elevation was then measured at 60, 120, and 240 min after Shenge administration. The ischemic size, serum levels of creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), and ST elevation were measured after the rats were sacrificed. Shenge decreased ST elevation induced by acute myocardial ischemia, reduced ischemic size, serum levels of CK-MB, LDH and MDA, and increased serum activity of SOD in a dose-dependent manner. The combined use of puerarin and Danshensu at a ratio of 1:1 showed the most effective activity. In conclusion, Shenge exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidant and anti-lipid peroxidation properties, and thus may be an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.

Hsia J, Criqui MH, Herrington DM, Manson JE, Wu L, Heckbert SR, Allison M, McDermott MM, Robinson J, Masaki K, Anonymous00166. · Department of Medicine, George Washington University, Washington, DC, USA. · Am Heart J. · Pubmed #16824852 No free full text.

Abstract: BACKGROUND: Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted. METHODS: The Estrogen Alone trial randomized 10739 postmenopausal women with prior hysterectomy, mean age 63.6 +/- 7.3 years, to conjugated equine estrogens (CEE 0.625 mg/d) or placebo and documented health outcomes over an average of 7.1 +/- 1.6 years. RESULTS: A trend toward increased risk of peripheral arterial events with CEE was observed (hazard ratio [HR] 1.32, 95% CI 0.99-1.77). Carotid arterial events (HR 1.19, 95% CI 0.82-1.74), lower extremity arterial events (HR 1.41, 95% CI 0.86-2.32), and abdominal aortic aneurysm (HR 2.40, 95% CI 0.92-6.23) were more frequent, but not individually significant, in the CEE group. However, the composite of lower extremity arterial disease/abdominal aortic aneurysm was significantly more frequent among women assigned to CEE (HR 1.63, 95 % CI 1.05-2.51). In subgroup analyses, no clear pattern of risk with CEE was apparent by age or by time since menopause. CONCLUSIONS: Unopposed CEE conferred no protection against peripheral arterial disease among generally healthy postmenopausal women; in fact, there was a suggestion of increased risk.

He H, Shi M, Zeng X, Yang X, Yang J, Wu L, Li L. · Institute of Chinese Herb Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, 310058, PRC. · Phytother Res. · Pubmed #18570278 No free full text.

Abstract: An increased propensity towards cardiac arrhythmias and aggravated heart function is observed in myocardial infarction (MI), the development of which is associated with the calcium handling system in the myocardium. It was hypothesized that the abnormal changes in the MI model may be a consequence of the abnormal expression and function of the RyR2-FKBP12.6 channel complex and that these abnormalities may be related to an over-activated endothelin (ET) system. Salvianolic acid B is expected to suppress life-threatening arrhythmias and to restore the abnormality of the RyR2-FKBP12.6 complex in rats. MI was produced by ligating the coronary artery for 4 weeks. Salvianolic acid B (100 mg/kg/day, p.o. for 4 weeks) was administered to rats 0.5 h before surgery. Measurements of cardiac arrhythmias, cardiac function, calcium transient, cardiac calcium release channel handling proteins and the endothelin system were conducted. The aggravated arrhythmia and compromised cardiac function in MI rats was accompanied by elevated diastolic Ca(2+) levels in the cytosol and a significant down-regulation of expression of RyR2-FKBP12.6. These were closely linked with an over-activated ET pathway in the myocardium. After a 4-week treatment with salvianolic acid B, all abnormalities were reversed significantly. Salvianolic acid B was capable of normalizing FKBP12.6 expression levels and decreasing the propensity towards arrhythmias by attenuating the up-regulated ET pathway.

He H, Shi M, Yang X, Zeng X, Wu L, Li L. · Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Zijingang Campus, Hangzhou, People's Republic of China. · Naunyn Schmiedebergs Arch Pharmacol. · Pubmed #18500511 No free full text.

Abstract: The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.

He H, Shi M, Yang J, Zeng X, Qiao H, Wu L, Li L. · Institute of Chinese Herbal Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. · Phytother Res. · Pubmed #18389490 No free full text.

Abstract: Emerging evidence indicates that angiogenesis may be a potential new target in treating heart failure (HF). It was hypothesized that a lack of angiogenesis would correlate with an abnormal expression of sarco/endoplasmic reticulum ATPase 2a (SERCA2a) and phospholamban (PLB), and the activated endothelin (ET) pathway and oxidative stress in HF. If this is the case, such normal changes could be reversed by puerarin. HF was produced by coronary artery ligation for 4 weeks in rats. The rats were divided into three groups: sham, HF untreated and HF + puerarin (120 mg/kg per day, i.p.). Hemodynamic and echocardiographic changes, angiogenesis, cardiac morphology, serum biochemistry, mRNA and proteins of the angiogenesis pathway, the ET pathway and redox were measured. In the HF rats, hemodynamic and echocardiographic abnormalities, cardiac remodeling and histological changes with features of cardiac failure were associated with a lack of the angiogenesis pathway, accompanied by oxidative stress, an up-regulated ET pathway and abnormal SERCA2a and PLB expressions in HF rats. Puerarin significantly promoted angiogenesis and reversed the above changes. In conclusion, the absence of the angiogenesis pathway correlated with abnormal expression of SERCA2a and PLB and an activated ET-ROS (reactive oxygen species) system in the affected myocardium. Puerarin promoted the angiogenesis pathway, improved myocardial microcirculation and down-regulated the ET system, resulting in a reversal of the abnormalities of expression of SERCA2a and PLB, and the cardiac performance in HF.

Wu L, Qiao H, Li Y, Li L. · College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China. · Phytother Res. · Pubmed #17450507 No free full text.

Abstract: Ischemic heart diseases are the leading cause of death in both developed and developing countries over the past decades. The aim of this study was to investigate the cardioprotective effects of the complex preparation (called Shenge), made of puerarin and Danshensu, on acute ischemic myocardial injury in rats and its underlying mechanisms. The left anterior descending (LAD) coronary artery was occluded to induce myocardial ischemia in hearts of SD rats. Shenge was injected into the tail vein 15 min after occlusion at doses of 0, 30, 60 or 120 mg/kg. Then, the ST elevation was measured at 60, 120 and 240 min after Shenge administration. The infarct size, serum levels of creatine kinase isoenzyme-MB (CK-MB), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA), and the ST elevation were measured after the rats were killed. Shenge decreased the ST elevation induced by acute myocardial ischemia, reduced infarct size, serum levels of CK-MB, LDH and MDA and increased the serum activity of SOD in a dose-dependent manner. The combined use of puerarin and Danshensu at a ratio of 1:1 shows the most effective activity. In conclusion, Shenge exerts significant cardioprotective effects against acute ischemic myocardial injury in rats, likely through its antioxidant and antilipid peroxidation properties, and thus may be used as an effective and promising medicine for both prophylaxis and treatment of ischemic heart disease.