RESUMO
The S100A1 gene is a promising target enhancing contractility and survival post myocardial infarction (MI). Achieving sufficient gene delivery within safety limits is a major translational problem. This proof of concept study evaluates viral mediated S100A1 overexpression featuring a novel liquid jet delivery (LJ) method. Twenty-four rats after successful MI were divided into three groups (n = 8 ea.): saline control (SA); ssAAV9.S100A1 (SS) delivery; and scAAV9.S100A1 (SC) delivery (both 1.2 × 10¹¹ viral particles). For each post MI rat, the LJ device fired three separate 100 µl injections into the myocardium. Following 10 weeks, all rats were evaluated with echocardiography, quantitative PCR (qPCR) and overall S100A1 and CD38 immune protein. At 10 weeks all groups demonstrated a functional decline from baseline, but the S100A1 therapy groups displayed preserved left ventricular function with significantly higher ejection fraction %; SS group (60 ± 3) and SC group (57 ± 4) versus saline (46 ± 3), P < 0.05. Heart qPCR testing showed robust S100A1 in the SS (10,147 ± 3993) and SC (35,155 ± 5808) copies per 100 ng DNA, while off-target liver detection was lower in both SS (40 ± 40), SC (34,841 ± 3164), respectively. Cardiac S100A1 protein expression was (4.3 ± 0.2) and (6.1 ± 0.3) fold higher than controls in the SS and SC groups, respectively, P < 0.05.
Assuntos
Técnicas de Transferência de Genes , Terapia Genética , Infarto do Miocárdio/terapia , Proteínas S100/genética , Animais , Dependovirus/genética , Vetores Genéticos , Masculino , Miocárdio/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas S100/biossíntese , Função Ventricular EsquerdaRESUMO
Congenital diaphragmatic hernia (CDH) is a rare condition. The aetiology of CDH is often unclear. In our case, a hollow mass was noted on MRI. Cardiac ejection fraction was diminished (47.0%) compared to 60.5% (average of 10 other normal animals, P < 0.05). The final diagnosis of congenital diaphragmatic hernia (Bochdalek type) was made when the sheep underwent surgery. The hernia was right-sided and contained the abomasum. Lung biopsy demonstrated incomplete development with a low number of bronchopulmonary segments and vessels. The likely cause of this hernia was genetic malformation.