Coronary Artery Disease: He H

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.

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, Yang F, Liu X, Zeng X, Hu Q, Zhu Q, Tu B. · Department of Cardiology, Qilu Hospital, University of Shandong, Jinan, China. · Menopause. · Pubmed #17108845 No free full text.

Abstract: OBJECTIVE: The goal of this study was to investigate the potential role of sex hormones in coronary atherosclerosis in both men and postmenopausal women. DESIGN: A total of 258 male and 236 female postmenopausal participants with angiographically defined stable coronary artery disease (CAD) were enrolled. We measured the levels of estradiol (E2), progesterone (P), testosterone (T), follicle-stimulating hormone, and luteinizing hormone in the participants and in 156 male and 132 female disease-free and age-matched controls using commercially available radioimmunoassay kits. RESULTS: In the male study participants and control subjects, the levels of E2 and P differed slightly in opposing directions; however, these differences were not significantly different, nor were there significant differences in T. However, the ratio of E2 to P in participants was significantly (P < 0.01) lower (even after adjustments for age and body mass index) than in the control subjects (mean +/- SEM: 70.2 +/- 56.4 vs 90.7 +/- 59.5, respectively). In the postmenopausal women, a slight decrease in E2 and increases in P and T in participants were not significantly different from levels in the control group. However, the E2 to P and E2 to T ratios were significantly (P < 0.01) lower (before and after adjustments for age and body mass index adjustments) in the participants relative to the control subjects (38.7 +/- 28.4 vs 49.6 +/- 36.3 and 46.5 +/- 37.6 vs 60.6 +/- 40.8, respectively). Correlation analyses demonstrated that the sex hormone ratio changes in both men and postmenopausal women were related with atherogenic blood lipoprotein changes. In both the male and female groups, levels of follicle-stimulating hormone and luteinizing hormone did not differ significantly between the participants and controls, and correlation analyses revealed no association between these hormones and the ratio of E2 to P in males and the ratios of E2 to P and E2 to T in females (r < 0.2, P > 0.05). Multiple regression analyses demonstrated that age and the presence of CAD were significantly and independently associated with the E2-to-P ratio in men and the E2-to-P and E2-to-T ratios in women and that E2-to-P ratio and low-density lipoprotein cholesterol level were significant independent predictors of CAD in males; E2-to-P and E2-to-T ratios and low-density lipoprotein cholesterol level were significant predictors of CAD in women. CONCLUSIONS: In both men and postmenopausal women with angiographic CAD, there were significant differences (relative to age-matched control subjects) in sex hormone ratios, suggesting an abnormality that could influence coronary health. A lower E2-to-P ratio may be associated with the male disposition to coronary atherosclerosis, whereas lower E2-to-P and E2-to-T ratios may be associated with the same condition in females.

Yang FL, He H, Liu XX, Tu B, Zeng XW, Su JX, Wang X, Hu Q. · Institute of Biochemistry and Molecular Biology, Medical College, Shandong University, Jinan 250012, China. · Acta Biochim Biophys Sin (Shanghai). · Pubmed #17091190 links to  free full text

Abstract: Caveolin-1 is regulated by estrogen in vascular smooth muscle cells. Raloxifene, a selective estrogen receptor modulator that possibly has cardioprotective properties without an increased risk of cancer or other side effects of estrogen, may be used in women with risk of coronary artery disease. However, the relationship between raloxifene and caveolin-1 is still unknown. Therefore, this study was designed to see whether raloxifene regulates caveolin-1 expression and if so, whether such regulation is mediated by estrogen receptor. Rat aortic smooth muscle cells were cultured in the absence or presence of raloxifene (10(8-) to 10(6-) M) for 12 or 24 h. Both mRNA and protein levels of caveolin-1 were increased significantly after 24 h treatment with raloxifene. These increases were inhibited by estrogen receptor antagonist ICI 182780 (10(5-) M). Results of this study suggest that raloxifene stimulates caveolin-1 transcription and translation through estrogen receptor mediated mechanisms.

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.