ABSTRACT
Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice.
Subject(s)
Bone Marrow Transplantation , Heart/physiopathology , Myocardial Infarction/therapy , Myocardium/metabolism , Transcriptome , Animals , Female , Gene Expression Profiling , Gene Expression Regulation , Inflammation Mediators/blood , Male , Mice , Mice, Inbred C57BL , Myocardial Infarction/immunology , Myocardial Infarction/metabolism , Myocardium/pathology , Oligonucleotide Array Sequence Analysis , Oxygen Consumption , Physical Exertion , Ventricular RemodelingABSTRACT
Despite cardiac metastases are found in about 20% of cancer deaths, the presence of primary cardiac tumors is rare. Most primary tumors are benign, and malignant tumors comprise about 15%. We report a 21-year-old man with fever, dyspnea, and hemoptysis that was diagnosed with angiosarcoma of the right atrium and pulmonary metastasis. Patient was submitted to surgical tumor resection without adjuvant therapy and died four months after diagnosis.
ABSTRACT
Objetivo: Avaliação do infarto do miocárdio (IM), induzido por isquemia e reperfusão em camundongos, por meio de análises ecocardiográficas, em equipamento específico para pequenos roedores. Medotologia: Camundongos machos e fêmeas C57BL/6 (oito semanas), pesando entre 20 e 25g, foram submetidos à indução do IM pelo protocolo isquemia e reperfusão (n=19), com um período de isquemia de 90 minutos e comparados a animais não infartados (n=10). Foram realizadas avaliações ecocardiográficas, antes do infarto e 8, 20 e 60 dias após a cirurgia com transdutor de alta resolução (30 MHz) específico para camundongos. Foram avaliados os diâmetros cavitários, fração de encurtamento pelo modo unidimensional e tempo de relaxamento isovolumétrico pelo Doppler, além de fração de ejeção calculada pelo método de Simpson, pelo modo bidimensional. Resultados: já na primeira análise, após o infarto do miocárdio, é possível evidenciar a dilatação do ventrículo esquerdo, em sístole (controle 2,10 +ou menos 0,43) mm versus infartado 2,83+ ou menos 0,46 mm, p<0,001) e diástole (controle 3,26+ ou menos 0,33 mm versus infartado 3,83 + ou menos 0,48 mm, p<0,01) e redução da fração de ejeção pelo método e Simpson (controle 74,63 + ou menos 8,29 versus infartado 62,58 + ou menos 11,62, p<0,05). Além disso, foi observado redução do tempo de relaxamento...