Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in MiceNovelty and Significance

Rationale: Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective: This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results: In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis ( P &lt;0.05). Conclusions: These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era. </jats:sec

Secondary Dyslipidemia In Obese Children - Is There Evidence For Pharmacological Treatment?

Abstract Background: Long-term safety, effectiveness and criteria for treatment with statins in children are still unclear in clinical practice. There is very limited evidence for the use of medication to treat children with dyslipidemia secondary to obesity who do not respond well to lifestyle modification. Objective: Systematic review of randomized clinical trials of statin use to treat children and adolescents with dyslipidemia secondary to obesity. Methods: We performed a search in PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO, and LILACS for data to evaluate the effect of statins on: improvement of surrogate markers of coronary artery disease in clinical outcomes of adulthood; increased serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipropotein B (APOB); and decreased serum levels of high-density lipoprotein cholesterol (HDL-C) from inception to February 2016. Participants were children and adolescents. Results: Of the 16793 potentially relevant citations recovered from the electronic databases, no randomized clinical trials fulfilled the inclusion criteria for children with dyslipidemia secondary to obesity. Conclusions: We found no specific evidence to consider statins in the treatment of hypercholesterolemia secondary to obesity in children. The usual practice of extrapolating findings from studies in genetic dyslipidemia ignores the differences in long-term cardiovascular risks and the long-term drug treatment risks, when compared to recommendation of lifestyle changes. Randomized clinical trials are needed to understand drug treatment in dyslipidemia secondary to obesity

Central hemodynamic parameters to predict cardiovascular outcomes and mortality among the elderly: protocol for a systematic review

ABSTRACT BACKGROUND: Central blood pressure is a factor that may predict cardiovascular events. However, its use in clinical practice is not well consolidated. Therefore, the aim of our study will be to summarize the use of central hemodynamic parameters to predict cardiovascular-related outcomes and all-cause mortality. DESIGN AND SETTING: Protocol for systematic review of longitudinal observational studies conducted in healthcare institutions, as presented in the studies included. METHODS: We will perform a systematic search in the electronic databases MEDLINE (via PubMed), EMBASE and LILACS (via Virtual Health Library (VHL)), using health descriptors terms for elderly people and for hemodynamic indices of central blood pressure. We will include articles that evaluated hemodynamic indices and at least one of the following outcomes: all-cause mortality, total cardiovascular death, total non-cardiovascular death, myocardial infarction, stroke, coronary artery restenosis after percutaneous coronary intervention, revascularization and aortic syndromes. Two independent reviewers will conduct analysis on the abstracts selected and on the full-text articles. Two reviewers will independently perform data extraction and evaluate the methodological quality of the articles selected, and a third reviewer will evaluate any divergences. The methodological quality of the studies will be assessed in accordance with the ROBINS-I tool (Risk Of Bias In Non-randomized Studies of Interventions). RESULTS AND CONCLUSIONS: Through this systematic review, we intend to summarize evidence that supports the use of central hemodynamic parameters for central blood pressure to diagnose and perform prognostics on arterial hypertension in elderly patients within clinical practice and predict future cardiovascular events in this population. REGISTRATION: Prospero - CRD42018085264

Effect of yerba mate and green tea on paraoxonase and leptin levels in patients affected by overweight or obesity and dyslipidemia: a randomized clinical trial

Abstract Background This study aimed to evaluate the effect of the intake of yerba mate (YM) and green tea (GT) on serum levels of leptin and paraoxonase-1 (PON-1), compared to control. Methods Controlled, randomized clinical trial (RCT) that evaluated 142 men and women affected by overweight or obesity aged 35–60 years, untreated dyslipidemia and no history of coronary artery disease. Participants were randomized to ingest 1000 mL GT, YM or apple tea (AT, control group) daily, during eight weeks. Serum PON-1 and leptin levels were analyzed by ELISA immunoassay at the beginning (baseline) and after eight weeks of intervention. Results The intake of 1 l of YM/day resulted in significant increase in serum levels of PON-1 (9.7%; p = 0.005). The consumption of GT induced no significant difference in the levels of PON-1 (p = 0.154) and leptin (p = 0.783). Intergroup analysis showed a significant difference (p = 0.036) in the variation of PON-1 levels in the YM group when compared to GT and AT groups. In addition, the increase in PON-1 levels in the YM group was significantly associated with increased HDL-c (p = 0.004). Conclusions The intake of yerba mate increased the antioxidant capacity by increasing serum levels of PON-1 and was positively associated with increased HDL-c, stressing the protective role of this beverage against atherosclerotic diseases. GT intake had no significant effect on serum levels of PON-1 and leptin. Trial registration This study is registered with ClinicalTrials.gov under protocol number NCT00933647

Cell Therapy in Ischemic Heart Disease: Interventions That Modulate Cardiac Regeneration

The incidence of severe ischemic heart disease caused by coronary obstruction has progressively increased. Alternative forms of treatment have been studied in an attempt to regenerate myocardial tissue, induce angiogenesis, and improve clinical conditions. In this context, cell therapy has emerged as a promising alternative using cells with regenerative potential, focusing on the release of paracrine and autocrine factors that contribute to cell survival, angiogenesis, and tissue remodeling. Evidence of the safety, feasibility, and potential effectiveness of cell therapy has emerged from several clinical trials using different lineages of adult stem cells. The clinical benefit, however, is not yet well established. In this review, we discuss the therapeutic potential of cell therapy in terms of regenerative and angiogenic capacity after myocardial ischemia. In addition, we addressed nonpharmacological interventions that may influence this therapeutic practice, such as diet and physical training. This review brings together current data on pharmacological and nonpharmacological approaches to improve cell homing and cardiac repair

Statin Treatments And Dosages In Children With Familial Hypercholesterolemia: Meta-Analysis

Abstract Background: Children with familial hypercholesterolemia may develop early endothelial damage leading to a high risk for the development of cardiovascular disease (CVD). Statins have been shown to be effective in lowering LDL cholesterol levels and cardiovascular events in adults. The effect of statin treatment in the pediatric population is not clearly demonstrated. Objective: To systematically review the literature to evaluate the effects of different statins and dosages in total cholesterol levels in children and adolescents with familial hypercholesterolemia. We also aimed to evaluate statin safety in this group. Methods: PubMed, EMBASE, Bireme, Web of Science, Cochrane Library, SciELO and LILACS databases, were searched for articles published from inception until February 2016. Two independent reviewers performed the quality assessment of the included studies. We performed a meta-analysis with random effects and inverse variance, and subgroup analyses were performed. Results: Ten trials involving a total of 1543 patients met the inclusion criteria. Our study showed reductions in cholesterol levels according to the intensity of statin doses (high, intermediate and low): (-104.61 mg/dl, -67.60 mg/dl, -56.96 mg/dl) and in the low-density lipoprotein cholesterol level: [-105.03 mg/dl (95% CI -115.76, -94.30), I2 19.2%], [-67.85 mg/dl (95% CI -83.36, -52.35), I2 99.8%], [-58.97 mg/dl (95% CI -67.83, -50.11), I2 93.8%. The duration of statin therapy in the studies ranged from 8 to 104 weeks, precluding conclusions about long-term effects. Conclusion: Statin treatment is efficient in lowering lipids in children with FH. There is need of large, long-term and randomized controlled trials to establish the long-term safety of statins

Mesenchymal stem cells from sternum : the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics

Background: In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. Methods: To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. Results: Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). Conclusions: Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics

Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics

Abstract Background In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. Methods To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. Results Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). Conclusions Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics

Mesenchymal stem cells from sternum : the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics

Background: In an attempt to increase the therapeutic potential for myocardial regeneration, there is a quest for new cell sources and types for cell therapy protocols. The pathophysiology of heart diseases may affect cellular characteristics and therapeutic results. Methods: To study the proliferative and differentiation potential of mesenchymal stem cells (MSC), isolated from bone marrow (BM) of sternum, we made a comparative analysis between samples of patients with ischemic (IHD) or non-ischemic valvular (VHD) heart diseases. We included patients with IHD (n = 42) or VHD (n = 20), with average age of 60 years and no differences in cardiovascular risk factors. BM samples were collected (16.4 ± 6 mL) and submitted to centrifugation with Ficoll-Paque, yielding 4.5 ± 1.5 × 107 cells/mL. Results: Morphology, immunophenotype and differentiation ability had proven that the cultivated sternal BM cells had MSC features. The colony forming unit-fibroblast (CFU-F) frequency was similar between groups (p = 0.510), but VHD samples showed positive correlation to plated cells vs. CFU-F number (r = 0.499, p = 0.049). The MSC culture was established in 29% of collected samples, achieved passage 9, without significant difference in expansion kinetics between groups (p > 0.05). Dyslipidemia and the use of statins was associated with culture establishment for IHD patients (p = 0.049 and p = 0.006, respectively). Conclusions: Together, these results show that the sternum bone can be used as a source for MSC isolation, and that ischemic or valvular diseases do not influence the cellular yield, culture establishment or in vitro growth kinetics

MOESM1 of Mesenchymal stem cells from sternum: the type of heart disease, ischemic or valvular, does not influence the cell culture establishment and growth kinetics

Additional file 1. Flow cytometry analysis of size and granularity (FFS x SSC) and staining of antibody-isotypes controls