Federica Del Monte

..SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca(2+) handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I/R...

..In conclusion, in DM failing hearts, SERCA2a gene transfer can increase coronary blood flow and reduce cardiomyocyte size without reduction in collagen production...

..We conclude that SERCA2a function enhanced by adenoviral gene transfer of asPLB prevents Ca2+ overload-induced LV contractile dysfunction in terms of mechanical work and especially energetics...

..Therefore enhancement of calcium handling either by resequestration into the SR or by intracellular buffering improves not only mechanical but energetic function in failing hearts...

..We inquired whether sarcoplasmic reticulum Ca2+ ATPase pump (SERCA2a) overexpression could reduce ischemic ventricular arrhythmias by modulating Ca2+ overload...

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..SERCA2a gene transfer transforms this inefficient energy utilization into a more efficient state and restores systolic and diastolic function to normal...

..3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway...

..001). Therefore, in a chronic model of MR, serial echocardiography demonstrated that MR begets MR and that those TD-derived indexes that initially increased post-MR decreased to baseline before any changes in LV ejection fraction...

..However, the interaction of CSCs with postmitotic myocytes results in the formation of cells with adult characteristics...

..The ability of the human heart to regenerate large quantities of myocytes remains controversial, and the extent of myocyte renewal claimed by different laboratories varies from none to nearly 20% per year...

..In addition, gene-based reconstitution of a normal phenotype allows us to closely examine the behavior of a large number of transcripts as the heart fails and is rescued by genetic manipulations...

..01) in the left ventricular wall and 0.91 +/- 0.1 vs. 0.66 +/- 0.07 ng (P </= 0.05) in the right ventricular wall. PAMGT with selective coronary venous blockade is feasible, reproducible, and safely achieved in a large-animal model...

..Understanding the mechanisms that regulate trafficking of human cardiac stem cells (hCSCs) may lead to development of new therapeutic approaches for the failing heart...

..In this review, we will examine our current understanding of these various factors. Gene transfer provides not only a potential therapeutic modality but also an approach to identifying and validating molecular targets...

..Thus, periostin and the pathway that it regulates may provide a target for innovative strategies to treat heart failure...

..We examined whether mitral regurgitation (MR) augments post-myocardial infarction (MI) remodeling...

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..This article reviews recent advances in gene delivery techniques aimed at global myocardial transfection and discusses molecular therapeutic targets identified within intracellular calcium signaling pathways in heart failure...

..This review focuses on the molecular characteristics of the pump, its role during the cardiac cycle and the prospects derived from the manipulation of SERCA2a for heart failure treatment...

..Gene transfer, which serves initially as an experimental tool, may provide a novel therapeutic approach...

..Furthermore, our approach to delivery of transgenes results in homogenous gene expression in both hypertrophied and failing hearts...

..In the brain of patients with dementia, proteinaceous aggregates and abnormal oligomeric assemblies of beta-amyloid impair cell function and lead to cell death...

..CONCLUSION: These results show that gene transfer of asPL can improve the contractile function in failing human myocardium. Targeting phospholamban may provide therapeutic benefits in human heart failure...

..These data demonstrate that PI3K-dependent but Akt-independent effectors are required for full cardioprotection and suggest a mechanism by which chronic Akt activation can become maladaptive...

..In this article, we will review the changes in calcium cycling that occur in myopathic hearts and how they can be effectively targeted. We will also focus on protein misfolding in the setting of cardiac dysfunction...

..The microarray analysis identified new genes following SERCA2a restoration in heart failure, which will give us insights into their role in the normalization of multiple pathways within the failing cell...

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..This imaging system may prove useful for the refinement of revascularization techniques, and for the administration of cardiac gene therapy...

..Here, we investigated the downstream phosphatidylinositol 3-kinase effector, serum- and glucocorticoid-regulated kinase-1 (SGK1), in heart failure and its complications...

..The turnover of cardiomyocytes in the aging female and male heart is currently unknown, emphasizing the need to define human myocardial biology...

..We found that chronic EPO treatment reduces MI size and improves cardiac function only at a dose that induces EPC mobilization in blood and that increases capillary density in the infarct border zone...

..The data also explain how late pregnancy poses a threat to cardiac homeostasis, and why pre-eclampsia and multiple gestation are important risk factors for the development of PPCM...

..Collectively, these data suggest that HRC may be an integral regulatory protein involved in cardiac muscle SR Ca uptake and Ca homeostasis...

..In conclusion, we provide the first evidence that increasing SERCA2a activity inhibits VSMC proliferation and balloon injury-induced neointima formation...

..Thus, PP1 is an important regulator of cardiac function, and inhibition of its activity may represent a novel therapeutic target in heart failure...

..Human heart sarcomeres coexpress 2 principal titin isoforms, a more compliant N2BA isoform and a stiffer N2B isoform. In comparison, normal rat hearts express almost no N2BA titin...

..We find no evidence for Ca(2+) overload induced by SERCA2a overexpression alone or in combination with catecholamines...

..Lessons gleaned from gene transfer experiments on local modulation of cardiac genetic programs will guide attempts to transform early investigations into established therapy...

..Thus, the inhibitor 1 of the type 1 phosphatase may represent an attractive new therapeutic target...

..Both SERCA2a overexpression and phospholamban down-regulation are effective strategies, and neither appears to produce supraphysiological stimulatory effects on contraction or relaxation...

..Elevated intracellular sodium concentrations can prolong the action potential duration, as well as the time course of muscle contraction, resulting in increased arrhythmogenesis...

..Collectively, our data suggest that HRC may play a key role in the regulation of SR Ca cycling through its direct interactions with SERCA2 and triadin, mediating a fine cross talk between SR Ca uptake and release in the heart...

..Additionally, in an animal model, physiologic growth concurrent with pathophysiologic hypertrophy induces similar changes in myocyte macroarchitecture but without the deleterious consequences for contractile function...

..Our observations further suggest for the first time ever novel targets for treatment of IDCM in women and men...

..4 x MLC.Luc) versus 1:1.4 (Ad.CMV.Luc). DISCUSSION: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart...

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