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Viviani Anselmi C.,Istituto Ricovero Cura Carattere Scientifico MultiMedica
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing | Year: 2010

PURPOSE: Several epidemiological published data support the protective role of omega-3 consumption in coronary artery disease, sudden cardiac death and ventricular arrhythmias, but interestingly, this is not the case for atrial arrhythmias. The purpose of this study is to evaluate different fatty acid profile between AF/AFL subjects and healthy controls. METHODS: Gas chromatography was employed to determine fatty acid percentage of erythrocyte membranes from 40 idiopathic AFL/AF patients and 53 healthy control subjects. RESULTS: AFL/AF erythrocyte membranes had significantly lower percentage of saturated fatty acid (43.1 +/- SD2.2 versus 47.8 +/- SD9.6, p < 0.001), monounsaturated fatty acid (18.2 +/- SD2.5 versus 22.6 +/- SD5.2, p < 0.001) and total trans fatty acid (0.2 +/- SD0.1 vs 1.3 +/- SD1.1, p < 0.001) than controls. Furthermore, fatty acid (FA) profiles of arrhythmic individuals showed an increased percent of total polyunsaturated fatty acid (PUFA) (36.7 +/- SD2.4 versus 26.4 +/- SD10.4, p < 0.001), PUFA n-3 (5.3 +/- SD1.1 versus 2.8 +/- SD1.8, p < 0.001) and n-6 (31.4 +/- SD2.2 versus 23.5 +/- SD9.9, p < 0.001). CONCLUSION: This study shows that the erythrocyte membranes FA composition of AF/AFL subjects differs from that of healthy controls.


Conneely K.N.,Emory University | Capell B.C.,Human Genome Research Institutes | Capell B.C.,University of Pennsylvania | Erdos M.R.,Human Genome Research Institutes | And 13 more authors.
Aging Cell | Year: 2012

A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4kb of the LMNA gene on a sample of long-lived individuals (LLI) (US Caucasians with age ≥95years, N=873) and genetically matched younger controls (N=443). We tested all common nonredundant haplotypes (frequency ≥0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on four SNPs, remained significant after adjustment for multiple testing (OR=1.56, P=2.5×10-5, multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3619 subjects from four independent samples of LLI and control subjects from (i) the New England Centenarian Study (NECS) (N=738), (ii) the Southern Italian Centenarian Study (SICS) (N=905), (iii) France (N=1103), and (iv) the Einstein Ashkenazi Longevity Study (N=702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR=1.60, P=0.0023), but not in the other three samples (P>0.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR=1.18, P=7.5×10-4, multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. © 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.


Rizzi R.,National Research Council Italy | Di Pasquale E.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | Di Pasquale E.,National Research Council Italy | Portararo P.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | And 13 more authors.
Cell Death and Differentiation | Year: 2012

Adult mammalian cells can be reprogrammed to a pluripotent state by forcing the expression of a few embryonic transcription factors. The resulting induced pluripotent stem (iPS) cells can differentiate into cells of all three germ layers. It is well known that post-natal cardiomyocytes (CMs) lack the capacity to proliferate. Here, we report that neonatal CMs can be reprogrammed to generate iPS cells that express embryonic-specific markers and feature gene-expression profiles similar to those of mouse embryonic stem (mES) cell and cardiac fibroblast (CF)-derived iPS cell populations. CM-derived iPS cells are able to generate chimeric mice and, moreover, re-differentiate toward CMs more efficiently then either CF-derived iPS cells or mES cells. The increased differentiation capacity is possibly related to CM-derived iPS cells retaining an epigenetic memory of the phenotype of their founder cell. CM-derived iPS cells may thus lead to new information on differentiation processes underlying cardiac differentiation and proliferation. © 2012 Macmillan Publishers Limited All rights reserved.


Anselmi C.V.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | Ferreri C.,CNR Institute for Organic Syntheses and Photoreactivity | Novelli V.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | Roncarati R.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | And 10 more authors.
Journal of Interventional Cardiac Electrophysiology | Year: 2010

Purpose Several epidemiological published data support the protective role of omega-3 consumption in coronary artery disease, sudden cardiac death and ventricular arrhythmias, but interestingly, this is not the case for atrial arrhythmias. The purpose of this study is to evaluate different fatty acid profile between AF/AFL subjects and healthy controls. Methods Gas chromatography was employed to determine fatty acid percentage of erythrocyte membranes from 40 idiopathic AFL/AF patients and 53 healthy control subjects. Results AFL/AF erythrocyte membranes had significantly lower percentage of saturated fatty acid (43.1±SD2.2 versus 47.8±SD9.6, p<0.001), monounsaturated fatty acid (18.2±SD2.5 versus 22.6±SD5.2, p<0.001) and total trans fatty acid (0.2±SD0.1 vs 1.3±SD1.1, p<0.001) than controls. Furthermore, fatty acid (FA) profiles of arrhythmic individuals showed an increased percent of total polyunsaturated fatty acid (PUFA) (36.7±SD2.4 versus 26.4±SD10.4, p<0.001), PUFA n-3 (5.3±SD1.1 versus 2.8±SD1.8, p< 0.001) and n-6 (31.4±SD2.2 versus 23.5±SD9.9, p<0.001). Conclusion This study shows that the erythrocyte membranes FA composition of AF/AFL subjects differs from that of healthy controls © Springer Science+Business Media, LLC 2010.


Bearzi C.,National Research Council Italy | Gargioli C.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | Baci D.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | Fortunato O.,Istituto Ricovero Cura Carattere Scientifico MultiMedica | And 6 more authors.
Cell death & disease | Year: 2014

Cell-based regenerative therapies are significantly improved by engineering allografts to express factors that increase vascularization and engraftment, such as placental growth factor (PlGF) and matrix metalloproteinase 9 (MMP9). Moreover, the seeding of therapeutic cells onto a suitable scaffold is of utmost importance for tissue regeneration. On these premises, we sought to assess the reparative potential of induced pluripotent stem (iPS) cells bioengineered to secrete PlGF or MMP9 and delivered to infarcted myocardium upon a poly(ethylene glycol)-fibrinogen scaffold. When assessing optimal stiffness of the PEG-fibrinogen (PF) scaffold, we found that the appearance of contracting cells after cardiogenic induction was accelerated on the support designed with an intermediate stiffness. Revascularization and hemodynamic parameters of infarcted mouse heart were significantly improved by injection into the infarct of this optimized PF scaffold seeded with both MiPS (iPS cells engineered to secrete MMP9) and PiPS (iPS cells engineered to secrete PlGF) cells as compared with nonengineered cells or PF alone. Importantly, allograft-derived cells and host myocardium were functionally integrated. Therefore, survival and integration of allografts in the ischemic heart can be significantly improved with the use of therapeutic cells bioengineered to secrete MMP9 and PlGF and encapsulated within an injectable PF hydrogel having an optimized stiffness.

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