Coronary Artery Disease: Shi M

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.

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.