Coronary Artery Disease: Yang X

Yang Y, Gruwel ML, Sun J, Gervai P, Yang X, Kupriyanov VV. · Institute for Biodiagnostics, National Research Council, Winnipeg, MB, Canada. · NMR Biomed. · Pubmed #18756440 No free full text.

Abstract: To assess infarction development in pig hearts, Mn-enhanced and Gd-enhanced MRI were used. In domestic pigs (25-35 kg, n = 37), the first and second diagonal branches of the left anterior descending coronary artery were ligated to induce acute ischemia and infarction (ischemia+reperfusion) or chronic infarction of increasing duration (3- 28 days). Ex vivo experiments were performed on hearts perfused in the Langendorff mode with a 50:50 mixture of blood and Krebs-Henseleit buffer using a spin-echo sequence on a 7 T Bruker imaging system. Signal acquisition from the heart and two reference test tubes (H(2)O and H(2)O + 10 mM CuSO(4)) was gated by the left ventricular pressure wave. T(1)-weighted images of six 8 mm short-axis slices (2 mm interslice gaps) were obtained before and after the addition of 0.2 mM MnCl(2) every 5 min over a 30-45 min period. Signal intensities were normalized to those of the H(2)O reference and fitted by a monoexponential function. The rates of intensity increase and maximal increases were significantly lower in the ischemic/infarcted areas and showed a trend to rise on infarction progression. In vivo Gd-enhanced MRI (3 T Siemens scanner) and in vivo/ex vivo near-infrared imaging confirmed major Mn-enhanced MRI findings. Triphenyltetrazolium chloride staining revealed necrotic areas in all chronic infarctions and no necrosis after acute ischemia. We conclude that MnCl(2) highlights ischemic areas because of the low collateral flow characteristic of pig hearts, whereas in the infarcted areas with substantial perfusion, scar tissue components are important for contrast distribution.

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.

Schadt EE, Molony C, Chudin E, Hao K, Yang X, Lum PY, Kasarskis A, Zhang B, Wang S, Suver C, Zhu J, Millstein J, Sieberts S, Lamb J, GuhaThakurta D, Derry J, Storey JD, Avila-Campillo I, Kruger MJ, Johnson JM, Rohl CA, van Nas A, Mehrabian M, Drake TA, Lusis AJ, Smith RC, Guengerich FP, Strom SC, Schuetz E, Rushmore TH, Ulrich R. · Rosetta Inpharmatics, Seattle, Washington, United States of America. · PLoS Biol. · Pubmed #18462017 links to  free full text

Abstract: Genetic variants that are associated with common human diseases do not lead directly to disease, but instead act on intermediate, molecular phenotypes that in turn induce changes in higher-order disease traits. Therefore, identifying the molecular phenotypes that vary in response to changes in DNA and that also associate with changes in disease traits has the potential to provide the functional information required to not only identify and validate the susceptibility genes that are directly affected by changes in DNA, but also to understand the molecular networks in which such genes operate and how changes in these networks lead to changes in disease traits. Toward that end, we profiled more than 39,000 transcripts and we genotyped 782,476 unique single nucleotide polymorphisms (SNPs) in more than 400 human liver samples to characterize the genetic architecture of gene expression in the human liver, a metabolically active tissue that is important in a number of common human diseases, including obesity, diabetes, and atherosclerosis. This genome-wide association study of gene expression resulted in the detection of more than 6,000 associations between SNP genotypes and liver gene expression traits, where many of the corresponding genes identified have already been implicated in a number of human diseases. The utility of these data for elucidating the causes of common human diseases is demonstrated by integrating them with genotypic and expression data from other human and mouse populations. This provides much-needed functional support for the candidate susceptibility genes being identified at a growing number of genetic loci that have been identified as key drivers of disease from genome-wide association studies of disease. By using an integrative genomics approach, we highlight how the gene RPS26 and not ERBB3 is supported by our data as the most likely susceptibility gene for a novel type 1 diabetes locus recently identified in a large-scale, genome-wide association study. We also identify SORT1 and CELSR2 as candidate susceptibility genes for a locus recently associated with coronary artery disease and plasma low-density lipoprotein cholesterol levels in the process.

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.

Liao D, Tan H, Hui R, Li Z, Jiang X, Gaubatz J, Yang F, Durante W, Chan L, Schafer AI, Pownall HJ, Yang X, Wang H. · Department of Medicine, Baylor College of Medicine, Houston, TX, USA. · Circ Res. · Pubmed #16931800 links to  free full text

Abstract: We previously reported that hyperhomocysteinemia (HHcy), an independent risk factor of coronary artery disease (CAD), is associated with increased atherosclerosis and decreased plasma high-density lipoprotein cholesterol (HDL-C) in cystathionine beta-synthase-/apolipoprotein E-deficient (CBS(-/-)/apoE(-/-)) mice. We observed that plasma homocysteine (Hcy) concentrations are negatively correlated with HDL-C and apolipoprotein A1 (apoA-I) in patients with CAD. We found the loss of large HDL particles, increased HDL-free cholesterol, and decreased HDL protein in CBS(-/-)/apoE(-/-) mice, and attenuated cholesterol efflux from cholesterol-loaded macrophages to plasma in CBS(-/-)/apoE(-/-) mice. ApoA-I protein was reduced in the plasma and liver, but hepatic apoA-I mRNA was unchanged in CBS(-/-)/apoE(-/-) mice. Moreover, Hcy (0.5 to 2 mmol/L) reduced the levels of apoA-I protein but not mRNA and inhibited apoA-1 protein synthesis in mouse primary hepatocytes. Further, plasma lecithin:cholesterol acyltransferase (LCAT) substrate reactivity was decreased, LCAT specific activity increased, and plasma LCAT protein levels unchanged in apoE(-/-)/CBS(-/-) mice. Finally, the clearance of plasma HDL cholesteryl ester, but not HDL protein, was faster in CBS(-/-)/apoE(-/-) mice, correlated with increased scavenger receptor B1, and unchanged ATP-binding cassette transporter A1 protein expression in the liver. These findings indicate that HHcy inhibits reverse cholesterol transport by reducing circulating HDL via inhibiting apoA-I protein synthesis and enhancing HDL-C clearance.

Yang X, Alexander KP, Chen AY, Roe MT, Brindis RG, Rao SV, Gibler WB, Ohman EM, Peterson ED, Anonymous00083. · Division of Cardiology and Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina 27715, USA. · J Am Coll Cardiol. · Pubmed #16226173 No free full text.

Abstract: OBJECTIVES: In a large contemporary population of patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), we sought to describe blood transfusion rates (overall and in patients who did not undergo coronary artery bypass grafting [CABG]), patient characteristics and practices associated with transfusion, variation among hospitals, and in-hospital outcomes in patients receiving transfusions. BACKGROUND: The use of antithrombotic agents and invasive procedures reduces ischemic complications but increases risks for bleeding and need for blood transfusion in patients with NSTE ACS. METHODS: We evaluated patient characteristics and transfusion rates in the overall population (n = 85,111) and determined outcomes and factors associated with need for transfusion in a subpopulation of patients who did not undergo CABG (n = 74,271) from 478 U.S. hospitals between January 1, 2001, and March 31, 2004. RESULTS: A total of 14.9% of the overall and 10.3% of the non-CABG population underwent transfusion during their hospitalization. Renal insufficiency and advanced age were strongly associated with the likelihood of transfusion. Interhospital transfusion rates varied significantly. Non-CABG patients who received transfusions had a greater risk of death (11.5% vs. 3.8%) and death or reinfarction (13.4% vs. 5.8%) than patients who did not undergo transfusion. CONCLUSIONS: Transfusion is common in the setting of NSTE ACS, and patients who undergo transfusion are sicker at baseline and experience a higher risk of adverse outcomes than their nontransfused counterparts. Given the wide variation in transfusion practice, further efforts to understand patient and process factors that result in bleeding and need for transfusion in NSTE ACS are needed.

Zou Y, Hu D, Yang X, Jia X, Wang L, Cui L, Liu X, Gao M, Wei Y, Xu Z. · Heart Center, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing 100020, China. · Chin Med J (Engl). · Pubmed #12875674 links to  free full text

Abstract: OBJECTIVE: To investigate the relationship among -75 bp/+83 bp polymorphism in apolipoprotein A1 (apo A1) gene, lipids levels and the occurrence of coronary atherosclerosis disease (CAD). METHODS: We determined distributions of two MspI polymorphisms of the apo A1 gene at -75 bp and +83 bp, and blood lipids levels among 137 Chinese patients (92 with CAD and 45 in the control group) in relation to circulating lipids and coronary angiography. RESULTS: The demographic information for 137 subjects showed that subjects with CAD tended to have more unfavorable lipoprotein variables. Genotype distributions at both sites were different between the CAD and control groups. Furthermore, the control group had higher M1-/M2- frequencies than the CAD group (M1: P < 0.005; M2: P < 0.05) and the "M1-" (A) and "M2-" alleles were associated with increased high-density lipoprotein cholesterol (HDL-C) (M1-: P < 0.0001; M2-: P < 0.05) and apo A1 (M1-: P < 0.0001; M2-: P < 0.05) levels. "M1-" and "M2-" were significantly negatively correlated with CAD (P < 0.01 and P < 0.05, respectively). CONCLUSIONS: Our results suggest that changes from G to A at the -75 bp site and from C to T or G to A at the +83 bp site do increase circulating levels of apo A1 and HDL-C. And those individuals with these changes are likely to have a lower risk of developing CAD.

Wu Q, Yu Q, Yang X. · Department of Cardiac Surgery, Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China. · Ann Thorac Surg. · Pubmed #12537206 No free full text.

Abstract: BACKGROUND: Double outlet right ventricle with L-malposition of the great arteries is a rare type of double outlet right ventricle. This article reviews our experience in treating this disease surgically. METHODS: Between September 1995 and May 1999, 9 patients with double outlet right ventricle [S, D, L] underwent modified Rastelli procedure at Fu Wai Hospital. In all patients, the two great arteries originated completely from the right ventricle. The malformation was associated with subaortic conus and L-transposition of the great arteries. The ventricular septal defect (VSD) was subpulmonary in 3 patients, and non-committed in 6. All but one patient had either pulmonary valvular stenosis or subpulmonary stenosis. No patient had any type of palliative operation before. A right ventriculotomy was made to repair the VSD with a Dacron or vascular prosthesitic patch, and an intraventricular tunnel was made between the left ventricle and the aorta. The main pulmonary artery was divided and the proximal end was closed. A homograft conduit was implanted between the inlet of the right ventricle and the main pulmonary artery. In the Rastelli procedure, the conduit is usually positioned between the right ventricular outflow tract and the pulmonary artery. RESULTS: All patients survived and recovered uneventfully. Echocardiography demonstrated that all intraventricular tunnels and valved conduits were functioning well. The results were satisfactory. CONCLUSIONS: Modified Rastelli procedure is an optimal method for surgically treating double outlet right ventricle with left-malposition of the great arteries. It can completely correct the right ventricular outflow tract stenosis, and right to left shunt, and avoid injuring the right coronary artery.

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.