<> "The repository administrator has not yet configured an RDF license."^^ . <> . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue"^^ . "ABSTRACT The mammalian heart is particularly susceptible to traumatic injury or sustained disease, suffering tissue deterioration, scarring and loss of contractile function. Clinical interventions to prevent or reverse the devastating effects of cardiac damage have met with limited success, presumably due to restricted cardiac regenerative potential. We tested the ability of a locally acting mIGF-1 isoform to regenerate the injured heart, restricting expression of a mIGF-1 transgene to the mouse myocardium to exclude endocrine effects on other tissues. Transgenic mIGF-1 hearts displayed accelerated postnatal cardiac growth that never exceeded the wild-type adult cardiac size. Early remodelling of the transgenic hearts was accompanied by transient activation of MAPKs and increased function of the translational machinery, without perturbing cardiac performance, and by modest upregulation of hypertrophic markers at one and two months. Notably, AKT the downstream effector of IGF-1 signalling was not activated in the hearts of transgenic mIGF-1 animals, indicating that a different kinase regulates mIGF-1 downstream signalling in the heart. The regenerative capacity of mIGF-1 was analyzed either by LAD ligation or by direct cardiotoxin (CTX) injection into the ventricles of adult mice. Injury to both wild-type and transgenic mIGF-1 hearts produced reproducible and localized infarctions coupled with early cell death and marked inflammation. In contrast to the characteristic progression of scar formation in wild-type hearts, transgenic mIGF-1 hearts induced complete repair of the injured tissue after 1 month, without scar formation. mIGF-1-induced regeneration was associated with a marked decrease in pro-inflammatory cytokines and an increase in anti-inflammatory cytokines, indicating that mIGF-1 drives regeneration in part by modulating the inflammatory response in pathological conditions. At later stages, mIGF-1 transgenic hearts displayed increased proliferative activity proximal to the infarct, and restored cardiac functionality. By enabling myocardial reconstruction following injury, the mIGF-1 isoform appears to bypass the evolutionary restrictions on mammalian regeneration. The enhancement of cardiac regeneration by localized expression of this growth factor suggests novel and clinically feasible therapeutic strategies to decrease inflammation and increase cell replacement after tissue damage."^^ . "2005" . . . . . . . . "Maria Paola"^^ . "Santini"^^ . "Maria Paola Santini"^^ . . . . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (PDF)"^^ . . . "Santini_thesis.pdf"^^ . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (Other)"^^ . . . . . . "indexcodes.txt"^^ . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (Other)"^^ . . . . . . "lightbox.jpg"^^ . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (Other)"^^ . . . . . . "preview.jpg"^^ . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (Other)"^^ . . . . . . "medium.jpg"^^ . . . "mIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue (Other)"^^ . . . . . . "small.jpg"^^ . . "HTML Summary of #7012 \n\nmIGF-1 regulates heart physiology and induces complete regeneration of infarcted myocardial tissue\n\n" . "text/html" . . . "570 Biowissenschaften, Biologie"@de . "570 Life sciences"@en . .