Bioinformatics analysis of circulating miRNAs related to cancer following spinal cord injury

Patients with spinal cord injury (SCI) have an increased risk of developing esophageal, bladder and hematologic malignancies compared with the normal population. In the present study, we aimed to identify, through in silico analysis, miRNAs and their target genes related to the three most frequent types of cancer in individuals with SCI. In a previous study, we reported a pattern of expression of miRNAs in 17 sedentary SCI males compared with 22 healthy able-bodied males by TaqMan OpenArray. This list of miRNAs deregulated in SCI patients was uploaded to miRWALK2.0 to predict the target genes and pathways of selected miRNAs. We used Cytoscape software to construct the network displaying the miRNAs and their gene targets. Among the down-regulated miRNAs in SCI, 21, 19 and 20 miRNAs were potentially associated with hematological, bladder and esophageal cancer, respectively, and three target genes (TP53, CCND1 and KRAS) were common to all three types of cancer. The three up-regulated miRNAs were potentially targeted by 18, 15 and 10 genes associated with all three types of cancer. Our current bioinformatics analysis suggests the potential influence of several miRNAs on the development of cancer in SCI. In general, these data may provide novel information regarding potential molecular mechanisms involved in the development of cancer among individuals with SCI. Further studies aiming at understanding how miRNAs contribute to the development of the major cancers that affect patients after SCI may help elucidate the role of these molecules in the pathophysiology of the disease.39CAPES - Coordenação de Aperfeiçoamento de Pessoal e Nível SuperiorFAPESP – Fundação de Amparo à Pesquisa Do Estado De São PauloSem informação2017/23563-

The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left ventricular mass in Brazilian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Reactive oxygen species have been implicated in the physiopathogenesis of hypertensive end-organ damage. This study investigated the impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular structure in Brazilian hypertensive subjects.</p> <p>Methods</p> <p>We cross-sectionally evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitória (n = 120)] by clinical history, physical examination, anthropometry, analysis of metabolic and echocardiography parameters as well as p22-phox C242T polymorphism genotyping. In addition, NADPH-oxidase activity was quantified in peripheral mononuclear cells from a subgroup of Campinas sample.</p> <p>Results</p> <p>Genotype frequencies in both samples were consistent with the Hardy- Weinberg equilibrium. Subjects with the T allele presented higher left ventricular mass/height^2.7than those carrying the CC genotype in Campinas (76.8 ± 1.6 vs 70.9 ± 1.4 g/m^2.7; p = 0.009), and in Vitória (45.6 ± 1.9 vs 39.9 ± 1.4 g/m^2.7; p = 0.023) samples. These results were confirmed by stepwise regression analyses adjusted for age, gender, blood pressure, metabolic variables and use of anti-hypertensive medications. In addition, increased NADPH-oxidase activity was detected in peripheral mononuclear cells from T allele carriers compared with CC genotype carriers (p = 0.03).</p> <p>Conclusions</p> <p>The T allele of the p22-phox C242T polymorphism is associated with higher left ventricular mass/height^2.7and increased NADPH-oxidase activity in Brazilian hypertensive patients. These data suggest that genetic variation within NADPH-oxidase components may modulate left ventricular remodeling in subjects with systemic hypertension.</p

How should treated hypertensive patients with systolic blood pressure below 120 mmHg be managed?

sem informação402520892090CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ306154/2017-

Leg Blood Pressure Measured in Orthostatic Posture Is Associated With Left Ventricular Mass in Normotensive Subjects

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)BACKGROUND Changing from a supine to an orthostatic posture is associated with substantial increments in leg blood pressure (BP) levels, which could ultimately influence the hemodynamic burden imposed on the heart. This study investigated the relationship between brachial and leg BP measurements and the left cardiac chamber's structure and assessed the role of body posture changes in this regard. METHODS One hundred and thirty normotensive, nondiabetic, nonsmoking, normolipemic subjects were evaluated by a clinical history, anthropometry, the analysis of metabolic parameters, echocardiography, and the measurement of BP in the arm and the calf in both supine and orthostatic positions. RESULTS Significant correlation coefficients between the leg BP measurements and the cardiac structure were detected, especially between the orthostatic pulse pressure (PP) and the left ventricular (LV) wall thickness (r = 0.38; P < 0.001), the orthostatic PP and the LV mass (r = 0.37; P < 0.001), and the orthostatic systolic BP (SBP) and the left atrial size (r = 0.35; P < 0.001). Stepwise and standard regression analysis adjusted for brachial BP and anthropometric and metabolic variables confirmed that the leg orthostatic PP was independently related to the LV wall thickness and mass. Moreover, the leg orthostatic SBP was associated with the left atrial dimension even after adding the LV mass to the statistical models. Finally, triglyceride levels and body surface area showed significant relationship with leg orthostatic PP and SBP, whereas brachial orthostatic PP and SBP were only associated with age and anthropometric variables. CONCLUSIONS Orthostatic leg BP is independently associated with the cardiac structure in normotensive subjects.251010831087Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Heart Failure And Midrange Ejection Fraction: Implications Of Recovered Ejection Fraction For Exercise Tolerance And Outcomes

Evidence-based therapies for heart failure (HF) differ significantly according to left ventricular ejection fraction (LVEF). However, few data are available on the phenotype and prognosis of patients with HF with midrange LVEF of 40% to 55%, and the impact of recovered systolic function on the clinical features, functional capacity, and outcomes of this population is not known. Methods and Results We studied 944 patients with HF who underwent clinically indicated cardiopulmonary exercise testing. The study population was categorized according to LVEF as follows: HF with reduced LVEF (HFrEF; LVEF55%; n=47). HF with midrange ejection fraction and no recovered ejection fraction and HF with recovered midrange ejection fraction had similar clinical characteristics, which were intermediate between those of HFrEF and HFpEF, and comparable values of predicted peak oxygen consumption and minute-ventilation/carbon dioxide production slope, which were better than HFrEF and similar to HFpEF. After a median of 4.4 (2.9-5.7) years, there were 253 composite events (death, left ventricular assistant device implantation, or transplantation). In multivariable Cox-regression analysis, HF with recovered midrange ejection fraction had lower risk of composite events than HFrEF (hazard ratio, 0.25; 95% confidence interval, 0.13-0.47) and HF with midrange ejection fraction and no recovered ejection fraction (hazard ratio, 0.31; 95% confidence interval, 0.15-0.67), and similar prognosis when compared with HFpEF. In contrast, HF with midrange ejection fraction and no recovered ejection fraction tended to show intermediate risk of outcomes in comparison with HFpEF and HFrEF, albeit not reaching statistical significance in fully adjusted analyses. Conclusions Patients with HF with midrange LVEF demonstrate a distinct clinical profile from HFpEF and HFrEF patients, with objective measures of functional capacity similar to HFpEF. Within the midrange LVEF HF population, recovered systolic function is a marker of more favorable prognosis.94National Heart. Lung, and Blood Institute [1K08HL116792-01A1]American Heart Association [14CRP20380422]Brazilian National Council for Scientific and Technological Development [249481/2013-8

Influence Of Cigarette Smoking On Cardiac Biomarkers: The Arherosclerosis Risk In Communities (aric) Study

Cigarette smoking has been associated with incident heart failure independent of coronary artery disease (CAD), but the mechanisms linking smoking to cardiac damage are not well understood. This study sought to evaluate the relationship between smoking and N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T (hs-TnT), which are, respectively, biomarkers of myocardial wall stress and injury, in a large community-based cohort. Methods and resultsWe examined the association between smoking history and NT-proBNP and hs-TnT in 9649 participants free of overt CAD or heart failure from the Atherosclerosis Risk in Communities (ARIC) Study who attended Visit 4 (1996-1998), as well as the association with change in these biomarkers from Visit 4 to Visit 5 (2011-2013) in 3151 participants. At Visit 4, higher cumulative cigarette exposure, assessed by total pack-years, was associated with elevated levels of NT-proBNP (P<0.001) and hs-TnT (P=0.01) among ever smokers in multivariable analyses adjusted for potential confounders. After 15years of follow-up, participants who were active smokers at Visit 4 had greater incidence of elevated NT-proBNP {adjusted proportion=48% [95% confidence interval (CI) 41, 54] vs. 35 (95% CI 32, 39); P=0.006} and hs-TnT [adjusted proportion=32% (95% CI 26, 38) vs. 23 (95% CI 20, 26); P=0.021] compared with never smokers, adjusting for baseline and follow-up covariates. ConclusionsIn a large community-based cohort free of overt CAD and heart failure, cigarette smoking was associated with biomarkers of myocardial wall stress and injury at baseline as well as with a continued measurable increase in these biomarkers after 15years of follow-up.186629637NHLBI NIH HHS [HHSN268201100005I, HHSN268201100005C, HHSN268201100005G, HHSN268201100006C, HHSN268201100007C, HHSN268201100007I, HHSN268201100008C, HHSN268201100008I, HHSN268201100009C, HHSN268201100009I, HHSN268201100010C, HHSN268201100011C, HHSN268201100011I, HHSN268201100012C, K08 HL116792, N01 HC055018, R00 HL107642

Smoking And Cardiac Structure And Function In The Elderly: The Aric Study (atherosclerosis Risk In Communities)

Cigarette smoking has been associated with higher risk of incident heart failure independent of coronary artery disease, but the impact of tobacco use on cardiac structure and function in the general population is uncertain. This study evaluated the relationship between smoking and echocardiographic measures in a large elderly cohort. Methods and Results We studied 4580 participants free of overt coronary artery disease, heart failure, and significant valvular disease from the fifth visit of the ARIC study (Atherosclerosis Risk in Communities) who underwent transthoracic echocardiography. Participants were classified into 3 categories based on self-reported smoking habits: never (43.2%), former (50.5%), and current smokers (6.3%). Pack-years and years of smoking were also estimated. Compared with never smokers, current smokers had greater left ventricular (LV) mass index (80.41.1 versus 76.7 +/- 0.4 g/m(2); P<0.001), LV mass/volume ratio (1.93 +/- 0.03 versus 1.83 +/- 0.03 g/mL; P<0.001), higher prevalence of LV hypertrophy (15% versus 9%; P=0.008), and worse diastolic function, as reflected by higher E/E ratio (11.7 +/- 0.2 versus 10.9 +/- 0.1; P<0.001), after adjusting for potential confounding factors. In contrast, former smokers showed similar echocardiographic features when compared with never smokers. Furthermore, estimated pack-years and years of smoking, measures of cumulative cigarette exposure, were associated with greater LV mass index, LV mass/volume ratio, and worse diastolic function (higher E/E ratio) in current smokers after multivariable analysis (all P<0.01). Conclusions Active smoking and cumulative cigarette exposure were associated with subtle alterations in LV structure and function in an elderly, community-based population free of overt coronary artery disease and heart failure.99National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100 007C, HHSN268201100008C, HHSN268201100009C, HHSN 268201100010C, HHSN268201100011C, HHSN268201100 012C]NHLBI [NHLBI-HC-11-08, R00-HL-107642, K08-HL-116792]Ellison FoundationPortuguese Foundation for Science and Technology [HMSP-ICS/007/2012]Brazilian National Council for Scientific and Technological Development Grant [249481/2013-8

Ambulatory blood pressure is associated with subclinical atherosclerosis in spinal cord injury subjects

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Ambulatory blood pressure phenotypes and isolated elevation of office central or brachial blood pressure

Disagreements in office brachial and central blood pressure (BP) have resulted in the identification of novel hypertension phenotypes, namely isolated central hypertension (ICH) and isolated brachial hypertension (IBH). This study investigated the relationship of ICH and IBH with ambulatory BP phenotypes among 753 individuals (mean age = 47.6 ± 15.2 years, 48% males) who underwent office and 24‐hours brachial and central BP measures using a Mobil‐O‐Graph PWA monitor. Thresholds for elevated office central and brachial BP were 130/90 and 140/90 mm Hg. Results of multivariable analysis adjusted for potential confounders showed that ICH (n = 25) had 3.71‐fold (95% CI 1.48‐9.32; P = .005) greater risk of masked hypertension than normal brachial/central BP (n = 362), while IBH (n = 20) had 4.65‐fold (95% CI 1.76‐12.25; P = .002) greater risk of white coat hypertension compared with combined brachial/central hypertension (n = 346). These findings suggest that the diagnosis of ICH and IBH might be useful in identifying individuals at higher risk of presenting discordant office and ambulatory BP phenotypes22101936194