Large-scale metabolomic profiling identifies novel biomarkers for incident coronary heart disease

Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.

Cardiac function in dogs with chronic Chagas cardiomyopathy undergoing autologous stem cell transplantation into the coronary arteries

This study assessed the effects of a single intracoronary injection of autologous stem cells on the cardiac function of dogs with Chagas cardiomyopathy. Bone-marrow-derived stem cells were delivered into the right and left coronary arteries of 5 mature dogs with mildly compromised cardiac function due to chronic Chagas cardiomyopathy. Blood pressure and electrocardiographic and echocardiographic parameters were recorded at monthly intervals for 6 mo in the 3 dogs that survived. Although no changes were observed in the electrocardiogram and blood pressure, there was a significant increase in peak velocity of aortic flow 3 mo after stem cell transplantation. Pre-ejection period, isovolumic relaxation time, and the Tei index of myocardial performance were reduced significantly 4 mo after the procedure. All significant changes persisted to the end of the study. The results suggest that the transplantation of autologous bone-marrow-derived stem cells into the coronary arteries of dogs with Chagas cardiomyopathy may have a beneficial effect but the small number of dogs studied was a limitation.

Intramyocardial course of the coronary arteries in the marsh deer (Blastocerus dichotomus)

O trajeto das artérias coronárias foi estudado no cervo-do-pantanal para comparação com os ruminantes domésticos. A artéria coronária esquerda se origina na aorta, na superfície auricular cardíaca e divide-se em ramos paraconal e circunflexo, os quais preenchem o sulco paraconal interventricular e sulco subsinuoso, respectivamente; esta artéria também origina um ramo para o conus arteriosus imediatamente antes de entrar no miocárdio. A artéria coronária direita surge da aorta, na borda cranial cardíaca e termina nesta borda, próximo ao sulco subsinuoso interventricular, entretanto, sem preenche-lo.

Haptoglobin polymorphism correlated with coronary artery disease

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Metabolic syndrome and dietary components are associated with coronary artery disease risk score in free-living adults: a cross-sectional study

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Respiratory pressures and expiratory peak flow rate of patients undergoing coronary artery bypass graft surgery

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Differential coronary resistance microvessel remodeling between type 1 and type 2 diabetic mice: Impact of exercise training

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Physiological importance of the coronary arterial blood supply to the rattlesnake heart

The reptilian heart consists of a thick inner spongy myocardium that derives its oxygen and nutrient supply directly from the blood within the ventricular cavity, which is surrounded by a thin outer compact layer supplied by coronary arteries. The functional importance of these coronary arteries remains unknown. In the present study we investigate the effects of permanent coronary artery occlusion in the South American rattlesnake (Crotalus durissus) on the ability to maintain heart rate and blood pressure at rest and during short term activity. We used colored silicone rubber (Microfil) to identify the coronary artery distribution and interarterial anastomoses. The coronary circulation was occluded and the snakes were then kept for 4 days at 30 degrees C. Microfil injections verified that virtually all coronary arteries had successfully been occluded, but also made visible an extensive coronary supply to the outer compact layer in untreated snakes. Electrocardiogram (ECG), blood pressure (P(sys)) and heart rate (f(H)) were measured at rest and during enforced activity at day 1 and 4. Four days after occlusion of the coronary circulation, the snakes could still maintain a P(sys) and f(H) of 5.2 +/- 0.2 kPa and 58.2 +/- 2.2 beats min(-1), respectively, during activity and the ECG was not affected. This was not different from sham-operated snakes. Thus, while the outer compact layer of the rattlesnake heart clearly has an extensive coronary supply, rattlesnakes sustain a high blood pressure and heart rate during activity without coronary artery blood supply.

Detection of Altered Risk Factors in Hospitalized Patients with Coronary Artery Disease

OBJECTIVE: To assess biochemical, anthropometric, and dietary variables considered risk factors for coronary artery disease. METHODS: Using anthropometrics, dietary allowance, and blood biochemistry, we assessed 84 patients [54 males (mean age of 55± 8 years) and 30 females (mean age of 57±7 years)], who had severe ( > or =70% coronary artery obstruction) and nonsevere forms of coronary artery disease determined by cardiac catheterization. The severe form of the disease prevailed in 70% of the males and 64% of the females, and a high frequency of familial antecedents (92% ' 88%) and history of acute myocardial infarction (80% ' 70%) were observed. Smoking predominated among males (65%) and diabetes mellitus among females (43%). RESULTS: Males and females had body mass index and body fat above the normal values. Females with nonsevere lesions had HDL > 35 mg/dL, and this constituted a discriminating intergroup indicator. Regardless of the severity of the disease, hyperglycemia and hypertriglyceridemia were found among females, and cholesterolemia > 200 mg/dL in both sexes, but only males had LDL fraction > 160 mg/dL and homocysteine > 11.7 mmol/L. The male dietary allowance was inadequate in nutrients for homocysteine metabolism and in nutrients with an antioxidant action, such as the vitamins B6, C, and folate. Individuals of both sexes had a higher lipid and cholesterol intake and an inadequate consumption of fiber. The diet was classified as high-protein, high-fat, and low-carbohydrate. CONCLUSION: The alterations found had no association with the severity of lesions, indicating the need for more effective nutritional intervention.

Modulation of coronary flow and cardiomyocyte size by sensory fibers

Cardiac tissue is densely innervated by sensory neurons that an believed to play important modulatory roles in cardiac functions. In this study, pretreatment of neonate mts with capsaicin was performed. In adult rats, cardiomyocyte size and amount of fibrous tissue in left ventricles as well as in vitro coronary flow were evaluated, the chronotropic and inotropic responses to beta-adrenoceptor agonists (norepinephrine and isoproterenol), muscarinic agonists (carbachol and pilocarpine), and calcitonin gene-related peptide (CGRP) were also investigated with the use of the isolated right atria preparation. Capsaicin pretreatment significantly (P<0.05) reduced both basal coronary flow (18% reduction) and cardiomyocyte size (34% reduction) without affecting the amount of fibrous tissues in the left ventricles. The positive inotropic and chronotropic effects in response to norepinephrine in the isolated rat heart did not significantly differ between control and capsaicin-treated rats, Similarly, the positive chronotropic effects in response to norepinephrine, isoproterenol, and CGRP as well as the negative chronotropic responses to carbachol and pilocarpine in the isolated light atria were not affected by capsaicin pretreatment, Our data are consistent with the suggestion that reductions of both basal coronary flow and cardiomyocyte size seen in hearts from capsaicin-pretreated rats may be consequences of CGRP depletion. The cardiomyocyte size reduction produced by capsaicin treatment may be related to a modulatory role of CGRP as a growth factor.