Effects of Cardiac Rehabilitation on Sleep Quality in Heart Disease Patients with and without Heart Failure

nsomnia is a modifiable cardiovascular risk factor. Previous studies suggested that attending a cardiac rehabilitation program may improve sleep quality in cardiac patients and pointed out the association between heart failure and poor sleep quality. The primary aim of this study was to evaluate sleep quality in patients attending a Multidisciplinary Cardiac Rehabilitation Program (MRCP), and to compare sleep quality between patients with and without heart failure. A prospective observational study was carried out on a consecutive sample of 240 patients attending an 8-week MRCP; 50 patients (20.8%) were included due to heart failure (NYHA stages I–III) and the rest of them after having undergone any revascularization procedure or valvular surgery. Before and after the completion of the MRCP, the quality of sleep was assessed by the Pittsburgh Sleep Quality Index (PSQI) score. Post-intervention global PSQI scores were statistically significantly lower than those of pre-intervention (p = 0.008), but only 60 patients (25%) registered a clinically significant improvement. When comparing patients with heart failure with those without, no differences in sleep quality were found. This suggests that only a small percentage of patients can achieve clinically significant improvements in sleep quality attending conventional MCRP. Suggestions for future research are given.Partial funding for open access charge: Universidad de Málag

Autoanticuerpos plaquetarios en la púrpura trombocitopénica idiopática y en la trombocitopenia asociada a la infección por el virus de la inmunodeficiencia humana / Rocío González-Conejero Hilla ; directores Vicente Vicente García, José Rivera Pozo.

Tesis-Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 447.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M.-1299

CALU polymorphism A29809G affects calumenin availability involving vascular calcification

Calumenin inhibits gamma-carboxylation of matrix-Gla-protein preventing BMP2-dependent calcification. Our aim was to explore the clinical relevance and functionality of the CALU polymorphism rs1043550, and the relationship of calumenin time-dependent expression profile with the active calcification of human vascular smooth muscle cells (hVSMC). Coronary artery calcium score and lesion severity were assessed by cardiac computed tomography in 139 consecutive low-risk patients genotyped for rs1043550. Polymorphic (G) allele carriage was associated with lower calcium (OR: 6.19, p= 0.042). Calcified arteries from CALU 'A' allele carriers undergoing cardiovascular surgery exhibited higher residual calcification, higher calumenin immunostaining and lower matrix-Gla-protein, contrary to 'G' allele carriers. In a luciferase reporter system in vascular cells, polymorphic 'G' allele reduced the mRNA stability by 30% (p<. 0.05). Osteogenic high-phosphate media induced active differentiation of hVSMC onto functional osteoblast-like cells as demonstrated by extracellular matrix mineralization and osteoblast markers expression. Calumenin was early over-expressed at day 3 (p<. 0.05), but decreased thereafter (mRNA and protein) with implications on gamma-carboxylation system. Calumenin was found released and co-localizing with extracellular matrix calcifications. The CALU polymorphism rs1043550 affects mRNA stability and tissue availability of calumenin thus supporting the protective clinical significance. Calumenin shows a time-dependent profile during induced calcification. These data demonstrate a novel association of vascular calcification with the VSMC phenotypic transition into osteoblast-like cells. Moreover, hyperphosphatemic stimuli render calumenin accumulation in the mineralized extracellular matrix. © 2015 Elsevier Ltd.This work was partially supported by the research projects: FFIS/CM10/013, FFIS-Caja Murcia Foundation; Spanish Society of Cardiology-Daiichi-Sankyo project 2012 and Abbott Vascular research grant; Spanish Ministerio de Economía y Competitividad (MINECO) (SAF2012-40127) and Instituto de Salud Carlos III (ISCIII) (Red de Investigación Cardiovascular [RD12/0042/0049 and RD12/0042/0053]. D. Hernández-Romero holds a postdoctoral research contract with IMIB-Arrixaca. E. Jover has a PhD research contract from the Instituto de Salud Carlos III. M. Quintana holds a research nurse contract with the IMIB-Arrixaca.Peer Reviewe

MicroRNAs as potential regulators of platelet function and bleeding diatheses

Although a growing number of studies suggest that microRNAs (miRNAs) play a relevant role in platelet biology, their implications in bleeding diatheses are starting to be investigated. Indeed, several studies have shown that alterations in the intracellular levels of highly expressed platelet miRNAs provoke a thrombotic phenotype. On the other hand, primary immune thrombocytopenia (ITP), which is considered the hallmark of acquired bleeding disorders, has been recently associated with altered levels of miRNAs in peripheral blood mononuclear cells, plasma, and platelets. In this review, we will focus on miRNAs that may affect the hemostatic and thrombotic functions of platelets, and we will discuss the different studies that have attempted to associate miRNAs with regulatory mechanisms of ITP

miR-146a deficiency in hematopoietic cells is not involved in the development of atherosclerosis.

BACKGROUND:Atherosclerosis involves activation of the IRAK1/TRAF6/NF-κB inflammatory cascade, which is negatively regulated by miR146a. Previous studies showed that the TT genotype of rs2431697, located near the miR-146a gene, drives lower miR-146a transcription and predicts adverse cardiovascular events in anticoagulated atrial fibrillation patients. Moreover, systemic miR-146a administration protects mice from atherosclerosis. Here we evaluated the ability of miR-146a expression in the hematopoietic component to regulate atherosclerosis in low-density lipoprotein receptor-null mice (Ldlr-/-). METHODS AND RESULTS:Lethally-irradiated Ldlr-/- mice transplanted with bone marrow from wild-type or miR-146a-null mice were fed an atherogenic diet for 8 and 20 weeks. Irak1, Traf6 and MIR146A expression were quantified in thoracic aorta by qRT-PCR and Western blot. Aortic plaque size and composition were characterized by Oil-Red staining and immunohistochemistry and leukocyte recruitment by intravital microscopy. Blood cell counts were similar in fat-fed Ldlr-/-mice with or without hematopoietic miR-146a expression. However, plasma cholesterol decreased in fat-fed Ldlr-/-mice transplanted with bone marrow deficient for miR-146a. Finally, aortic atherosclerosis burden and recruitment of leukocytes into the vessel wall were undistinguishable between the two groups, despite higher levels of Irak1 and Traf6 mRNA and protein in the aorta of fat-fed mice lacking hematopoietic miR-146a expression. CONCLUSIONS:miR-146a deficiency exclusively in hematopoietic cells modulates cholesterol levels in plasma and the expression of its targets in the artery wall of fat-fed Ldlr-/- mice, but does not accelerate atherosclerosis. Atheroprotection upon systemic miR-146a administration may therefore be caused by specific effects on vascular cells

MicroRNAs as New Regulators of Neutrophil Extracellular Trap Formation

Neutrophil extracellular traps (NETs) are formed after neutrophils expelled their chromatin content in order to primarily capture and eliminate pathogens. However, given their characteristics due in part to DNA and different granular proteins, NETs may induce a procoagulant response linking inflammation and thrombosis. Unraveling NET formation molecular mechanisms as well as the intracellular elements that regulate them is relevant not only for basic knowledge but also to design diagnostic and therapeutic tools that may prevent their deleterious effects observed in several inflammatory pathologies (e.g., cardiovascular and autoimmune diseases, cancer). Among the potential elements involved in NET formation, several studies have investigated the role of microRNAs (miRNAs) as important regulators of this process. miRNAs are small non-coding RNAs that have been involved in the control of almost all physiological processes in animals and plants and that are associated with the development of several pathologies. In this review, we give an overview of the actual knowledge on NETs and their implication in pathology with a special focus in cardiovascular diseases. We also give a brief overview on miRNA biology to later focus on the different miRNAs implicated in NET formation and the perspectives opened by the presented data

Prognostic and Predictive Effects of Tumor and Plasma miR-200c-3p in Locally Advanced and Metastatic Breast Cancer

While the role of miR-200c in cancer progression has been established, its expression and prognostic role in breast cancer is not completely understood. The predictive role of miR-200c in response to chemotherapy has also been suggested by some studies, but only limited clinical evidence is available. The purpose of this study was to investigate miR-200c-3p in the plasma and primary tumor of BC patients. The study design included two cohorts involving women with locally advanced (LABC) and metastatic breast cancer. Tumor and plasma samples were obtained before and after treatment. We found that miR-200c-3p was significantly higher in the plasma of BC patients compared with the controls. No correlation of age with plasma miR-200c-3p was found for controls or for BC patients. MiR-200c-3p tumor expression was also associated with poor overall survival in LABC patients treated with neoadjuvant chemotherapy, independently of pathological complete response or clinical stage. Our findings suggest that plasmatic miR-200c-3p levels could be useful for BC staging, while the tumor expression of miR-200c-3p might provide further prognostic information beyond residual disease in BC treated with neoadjuvant chemotherapy

Schematic diagrams of human mRNA of <i>HNF4A</i>.

<p>[<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154751#pone.0154751.ref027" target="_blank">27</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154751#pone.0154751.ref028" target="_blank">28</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0154751#pone.0154751.ref030" target="_blank">30</a>]</p