Biological significance of miR-126 expression in atrial fibrillation and heart failure

We investigated the biological significance of microRNA-126 (miR-126) expression in patients with atrial fibrillation (AF) and/or heart failure (HF) to examine the possible mechanism of miR-126-dependent AF and development of HF. A total of 103 patients were divided into three groups: AF group (18 men and 17 women, mean age: 65.62±12.72 years), HF group (17 men and 15 women, mean age: 63.95±19.71 years), and HF-AF group (20 men and 16 women, mean age: 66.56±14.37 years). Quantitative real-time PCR was used to measure relative miR-126 expression as calculated by the 2−ΔΔCt method. miR-126 was frequently downregulated in the 3 patient groups compared with controls. This reduction was significantly lower in permanent and persistent AF patients than in those with paroxysmal AF (P<0.05, t-test). Moreover, miR-126 expression was markedly lower in the HF-AF group compared with the AF and HF groups. The 3 patient groups had higher N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels, lower left ventricular ejection fraction (LVEF), larger left atrial diameter, and higher cardiothoracic ratio compared with controls. There were significant differences in NT-proBNP levels and LVEF among the AF, HF, and HF-AF groups. Pearson correlation analysis showed that relative miR-126 expression was positively associated with LVEF, logarithm of NT-proBNP, left atrial diameter, cardiothoracic ratio, and age in HF-AF patients. Multiple linear regression analysis showed that miR-126 expression was positively correlated with LVEF, but negatively correlated with the logarithm of NT-pro BNP and the cardiothoracic ratio (all P<0.05). Serum miR-126 levels could serve as a potential candidate biomarker for evaluating the severity of AF and HF. However, to confirm these results, future studies with a larger and diverse patient population are necessary.

Overexpression of myeloid differentiation protein 88 in mice induces mild cardiac dysfunction, but no deficit in heart morphology

Cardiac remodeling involves changes in heart shape, size, structure, and function after injury to the myocardium. The proinflammatory adaptor protein myeloid differentiation protein 88 (MyD88) contributes to cardiac remodeling. To investigate whether excessive MyD88 levels initiate spontaneous cardiac remodeling at the whole-organism level, we generated a transgenic MyD88 mouse model with a cardiac-specific promoter. MyD88 mice (male, 20-30 g, n=∼80) were born at the expected Mendelian ratio and demonstrated similar morphology of the heart and cardiomyocytes with that of wild-type controls. Although heart weight was unaffected, cardiac contractility of MyD88 hearts was mildly reduced, as shown by echocardiographic examination, compared with wild-type controls. Moreover, the cardiac dysfunction phenotype was associated with elevation of ANF and BNP expression. Collectively, our data provide novel evidence of the critical role of balanced MyD88 signaling in maintaining physiological function in the adult heart.

Correlation between heart rate variability and pulmonary function adjusted by confounding factors in healthy adults

The autonomic nervous system maintains homeostasis, which is the state of balance in the body. That balance can be determined simply and noninvasively by evaluating heart rate variability (HRV). However, independently of autonomic control of the heart, HRV can be influenced by other factors, such as respiratory parameters. Little is known about the relationship between HRV and spirometric indices. In this study, our objective was to determine whether HRV correlates with spirometric indices in adults without cardiopulmonary disease, considering the main confounders (e.g., smoking and physical inactivity). In a sample of 119 asymptomatic adults (age 20-80 years), we evaluated forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). We evaluated resting HRV indices within a 5-min window in the middle of a 10-min recording period, thereafter analyzing time and frequency domains. To evaluate daily physical activity, we instructed participants to use a triaxial accelerometer for 7 days. Physical inactivity was defined as <150 min/week of moderate to intense physical activity. We found that FVC and FEV1, respectively, correlated significantly with the following aspects of the RR interval: standard deviation of the RR intervals (r =0.31 and 0.35), low-frequency component (r =0.38 and 0.40), and Poincaré plot SD2 (r =0.34 and 0.36). Multivariate regression analysis, adjusted for age, sex, smoking, physical inactivity, and cardiovascular risk, identified the SD2 and dyslipidemia as independent predictors of FVC and FEV1 (R2=0.125 and 0.180, respectively, for both). We conclude that pulmonary function is influenced by autonomic control of cardiovascular function, independently of the main confounders.

Deficiency of sex hormones does not affect 17-ß-estradiol-induced coronary vasodilation in the isolated rat heart

The relaxation of coronary arteries by estrogens in the coronary vascular beds of naive and hypertensive rats has been well described. However, little is known about this action in gonadectomized rats. We investigated the effect of 17-ß-estradiol (E2) in coronary arteries from gonadectomized rats, as well as the contributions of endothelium-derived factors and potassium channels. Eight-week-old female and male Wistar rats weighing 220-300 g were divided into sham-operated and gonadectomized groups (n=9−12 animals per group). The baseline coronary perfusion pressure (CPP) was determined, and the vasoactive effects of 10 μM E2 were assessed by bolus administration before and after endothelium denudation or by perfusion with NG-nitro-L-arginine methyl ester (L-NAME), indomethacin, clotrimazole, L-NAME plus indomethacin, L-NAME plus clotrimazole or tetraethylammonium (TEA). The CPP differed significantly between the female and sham-operated male animals. Gonadectomy reduced the CPP only in female rats. Differences in E2-induced relaxation were observed between the female and male animals, but male castration did not alter this response. For both sexes, the relaxation response to E2 was, at least partly, endothelium-dependent. The response to E2 was reduced only in the sham-operated female rats treated with L-NAME. However, in the presence of indomethacin, clotrimazole, L-NAME plus indomethacin or L-NAME plus clotrimazole, or TEA, the E2 response was significantly reduced in all groups. These results highlight the importance of prostacyclin, endothelium-derived hyperpolarizing factor, and potassium channels in the relaxation response of coronary arteries to E2 in all groups, whereas nitric oxide may have had an important role only in the sham-operated female group.

Histidine-tryptophan-ketoglutarate solution decreases mortality and morbidity in high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease: an 11-year experience from a single institution

Cardioplegic reperfusion during a long term ischemic period interrupts cardiac surgery and also increases cellular edema due to repeated solution administration. We reviewed the clinical experiences on myocardial protection of a single perfusion with histidine-tryptophan-ketoglutarate (HTK) for high-risk patients with severe pulmonary arterial hypertension associated with complex congenital heart disease. This retrospective study included 101 high-risk patients undergoing arterial switch operation between March 2001 and July 2012. We divided the cohort into two groups: HTK group, myocardial protection was carried out with one single perfusion with HTK solution; and St group, myocardial protection with conventional St. Thomas' crystalloid cardioplegic solution. The duration of cardiopulmonary bypass did not differ between the two groups. The mortality, morbidity, ICU stay, post-operative hospitalization time, and number of transfusions in HTK group were lower than those in St group (P<0.05). Univariate and multivariate analysis showed that HTK is a statistically significant independent predictor of decreased early mortality and morbidity (P<0.05). In conclusion, HTK solution seems to be an effective and safe alternative to St. Thomas' solution for cardioplegic reperfusion in high-risk patients with complex congenital heart disease.

The validation of heart rate variability in individuals with spinal cord injury

The current classification system for spinal cord injury (SCI) considers only somatic information and neglects autonomic damage after injiuy. Heart rate variability (HRV) has the potential to be a valuable measure of cardiac autonomic control after (SCI). Five individuals with tetraplegia and four able-bodied controls underwent 1 min continuous ECG recordings during rest, after Metoprolol administration (max dose=3x5mg) and after Atropine administration (0.02mg/kg) in both supine and 40° head-up tilt. After Metoprolol administration there was a 61.8% decrease in the LF:HF ratio in the SCI participants suggesting that the LF:HF ratio is a reflection of cardiac sympathetic outflow. After Atropine administration there was a 99.1% decrease in the HF power in the SCI participants suggesting that HF power is highly representative of cardiac parasympathetic outflow. There were no significant differences between the SCI and able-bodied participants. Thus, HRV measures are a valid index of cardiac autonomic control after SCI.

Comparative study of bovine heart and bacillus subtilis cytochrome c oxidase vesicles and the influence of bulk pH on cytochrome c oxidase components

Studies on the steady state behavior of soluble cytochrome c oxidase are extensive. These studies have examined the influence of ionic strength and pH and may provide answers to questions such as the link between proton translocation and charge separation. The present study examined the influence of external bulk pH on ApH formation, biphasic kinetics, and steady state reduction of cytochromes c and a of cytochrome c oxidase in proteoliposomes. Bulk pH has an appreciable effect on ApH formation and steady state reduction levels of cytochromes c and 8. Bulk pH affected total Vmax and Km at the low affinity binding site of cytochrome c. This study also examined the influence of bovine serum albumin and free fatty acids on proton pumping activity in bovine heart proteoliposomes. Proton pumping activity decreased after treatment with BSA, and was subsequently reinstated after further treatment with FFA. Much study in the superfamily of haem/copper oxidases has recently been devoted to the bacterial oxidases. The present study has examined some protein composition characteristics and bioenergetic features of Bacillus subtilis cytochrome caa3 oxidase. Results provide evidence for the structural composition of the enzyme in relation to the covalently bound cytochrome c to the oxidas~. Bioenergetically, caa3 COV showed appreciable proton pumping activity. Steady state analysis of the caa3 COV showed significantly different cytochrome c and a reduction characteristics compared to the bovine enzyme.

Comparison of non-HDL cholesterol and waist circumference vs. triglyceride levels and waist circumference in predicting coronary heart disease risk

BACKGROUND: Dyslipidemia is recognized as a major cause of coronary heart disease (CHD). Emerged evidence suggests that the combination of triglycerides (TG) and waist circumference can be used to predict the risk of CHD. However, considering the known limitations of TG, non-high-density lipoprotein (non-HDL = Total cholesterol - HDL cholesterol) cholesterol and waist circumference model may be a better predictor of CHD. PURPOSE: The Framingham Offspring Study data were used to determine if combined non-HDL cholesterol and waist circumference is equivalent to or better than TG and waist circumference (hypertriglyceridemic waist phenotype) in predicting risk of CHD. METHODS: A total of3,196 individuals from Framingham Offspring Study, aged ~ 40 years old, who fasted overnight for ~ 9 hours, and had no missing information on nonHDL cholesterol, TG levels, and waist circumference measurements, were included in the analysis. Receiver Operator Characteristic Curve (ROC) Area Under the Curve (AUC) was used to compare the predictive ability of non-HDL cholesterol and waist circumference and TG and waist circumference. Cox proportional-hazards models were used to examine the association between the joint distributions of non-HDL cholesterol, waist circumference, and non-fatal CHD; TG, waist circumference, and non-fatal CHD; and the joint distribution of non-HDL cholesterol and TG by waist circumference strata, after adjusting for age, gender, smoking, alcohol consumption, diabetes, and hypertension status. RESULTS: The ROC AUC associated with non-HDL cholesterol and waist circumference and TG and waist circumference are 0.6428 (CI: 0.6183, 0.6673) and 0.6299 (CI: 0.6049, 0.6548) respectively. The difference in the ROC AVC is 1.29%. The p-value testing if the difference in the ROC AVCs between the two models is zero is 0.10. There was a strong positive association between non-HDL cholesterol and the risk for non-fatal CHD within each TO levels than that for TO levels within each level of nonHDL cholesterol, especially in individuals with high waist circumference status. CONCLUSION: The results suggest that the model including non-HDL cholesterol and waist circumference may be superior at predicting CHD compared to the model including TO and waist circumference.