RESUMO
INTRODUCTION: Thoracic aortic aneurysms and dissections (TAAD) are rare in children and often associated with underlying genetic disorders accompanied with other systemic manifestations, including connective or osteo-articular tissue diseases. CASE PRESENTATION: We report the case of a 10-year-old girl with a novel nonsense SMAD3 mutation, p.Glu102X, who presented with familial TAAD without any signs of osteoarthritis. Histological analysis of aorta fragments from the patient with TAAD obtained during surgery revealed elastin degradation and inflammatory infiltration of T cells with dense CD31 + microvessels, which is consistent with previous findings. Interestingly, the family members with the SMAD3 mutation developed IgA nephropathy. CONCLUSION: Because the TGF-ß/Smad signalling pathway plays an important role in the primary pathogenesis of IgA nephropathy and TAAD, we presume that IgA nephropathy could be a novel clinical phenotype of SMAD3 deficiency. Further accumulation of genetically proven cases with SMAD3 deficiency is needed to more accurately characterize phenotypic variability and elucidate a wide spectrum of TGF-ß-associated disorders.
Assuntos
Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Proteína Smad3/genética , Dissecção Aórtica/diagnóstico , Aneurisma da Aorta Torácica/diagnóstico , Criança , Códon sem Sentido , Feminino , Humanos , LinhagemRESUMO
BACKGROUNDS: Salusins are multifunctional endogenous bioactive peptides simultaneously biosynthesized from their precursor prosalusin. Salusin-ß stimulates proliferation of vascular smooth muscle cells and fibroblasts and regulates myocardial growth and hypertrophy. Salusin-ß has potent hypotensive, bradycardic and proatherosclerotic effects. OBJECTIVES: To investigate whether salusin-ß plays a role in myocardial remodeling after myocardial ischemia reperfusion (I/R) injury, rat I/R models were created by the left anterior descending coronary artery occlusion for 30 min, followed by 24 h or 7 days of reperfusion (control, n = 6 each). RESULTS AND CONCLUSION: Immunohistochemical double staining showed the enhanced expression of salusin-ß in the macrophages around myocardial ischemic area. Anti-salusin-ß treated groups were administered the neutralizing salusin-ß antibody (10 µl/day, i.p.) once daily from day -1 to day 1 or from day -1 to day 7 (anti-salusin-ß, n = 6 each). The anti-salusin-ß therapy enhanced myocardial angiogenesis in the peri-ischemic area of reperfusion. The small vessels (< 40 µm in diameter) of I/R hearts treated with anti-salusin-ß were more densely populated than those of control animals (108.5 ± 19.7 vs 47.5 ± 2.4, p < 0.05). Real-time PCR revealed that the anti-salusin-ß therapy-induced angiogenesis was not associated with enhanced vascular endothelial growth factor A expression. The authors, for the first time, have clarified that endogenous salusin-ß suppresses angiogenesis which is critical in the development of cardiac remodeling following I/R injury.
Assuntos
Anticorpos/uso terapêutico , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Animais , Anticorpos/farmacologia , Linhagem Celular , Células Cultivadas , Quimiocina CCL2/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Neovascularização Fisiológica/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND: MMP activity is upregulated in the heart after myocardial ischemia reperfusion, and its activation contributes to the changes in left ventricular (LV) dysfunction. A major macrolide antibiotic, clarithromycin has many biological functions including MMP regulation. However, little is known about the effect of clarithromycin in myocardial reperfusion injury via MMPs. Our objective was to clarify the role of MMPs regulated by clarithromycin in the progression of myocardial reperfusion injury. METHODS: We administered clarithromycin to rats with ischemia-reperfusion injury twice a day for 7 days before and 14 days after reperfusion. RESULTS: Clarithromycin resulted in a significant reduction of the infarction area:area at risk ratio and preserved fractional shortening ratio after 14 days of reperfusion. Immunohistochemical analysis revealed that macrophages were the primary cellular source of MMPs. Fewer macrophages were detected in the ischemic area of the hearts following ischemia reperfusion in the clarithromycin-treated group compared with the vehicle-treated group. Although ischemia-reperfusion injury resulted in LV fibrosis with increasing MMP activities, clarithromycin significantly reduced these changes. CONCLUSION: Clarithromycin is effective for attenuating myocardial ischemia-reperfusion injury by suppressing MMPs.