RESUMO
Pulmonary arterial hypertension (PAH) is a progressive disease which causes right ventricular (RV) failure. Canstatin, a C-terminal fragment of type IV collagen α2 chain, is expressed in various rat organs. However, the expression level of canstatin in plasma and organs during PAH is still unclear. We aimed to clarify it and further investigated the protective effects of canstatin in a rat model of monocrotaline-induced PAH. Cardiac functions were assessed by echocardiography. Expression levels of canstatin in plasma and organs were evaluated by enzyme-linked immunosorbent assay and Western blotting, respectively. PAH was evaluated by catheterization. RV remodeling was evaluated by histological analyses. Real-time polymerase chain reaction was performed to evaluate RV remodeling-related genes. The plasma concentration of canstatin in PAH rats was decreased, which was correlated with a reduction in acceleration time/ejection time ratio and an increase in RV weight/body weight ratio. The protein expression of canstatin in RV, lung and kidney was decreased in PAH rats. While recombinant canstatin had no effect on PAH, it significantly improved RV remodeling, including hypertrophy and fibrosis, and prevented the increase in RV remodeling-related genes. We demonstrated that plasma canstatin is decreased in PAH rats and that administration of canstatin exerts cardioprotective effects.
Assuntos
Cardiotônicos/uso terapêutico , Colágeno Tipo IV/biossíntese , Colágeno Tipo IV/uso terapêutico , Hipertensão Pulmonar/metabolismo , Fragmentos de Peptídeos/uso terapêutico , Remodelação Ventricular/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Colágeno Tipo IV/sangue , Colágeno Tipo IV/genética , Avaliação Pré-Clínica de Medicamentos , Ensaio de Imunoadsorção Enzimática , Fibrose , Ventrículos do Coração/efeitos dos fármacos , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/genética , Hipertrofia , Rim/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Monocrotalina/toxicidade , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Wistar , Proteínas Recombinantes/uso terapêuticoRESUMO
We have developed a femtosecond high-intensity laser system that combines both Ti:sapphire chirped-pulse amplification (CPA) and optical parametric CPA (OPCPA) techniques and produces more than 30 J broadband output energy, indicating the potential for achieving peak powers in excess of 500 TW. With a cleaned high-energy seeded OPCPA preamplifier as a front end in the system, for the compressed pulse without pumping the final amplifier, we found that the temporal contrast in this system exceeds 10(10) on the subnanosecond time scales, and is near 10(12) on the nanosecond time scale prior to the peak of the main femtosecond pulse. Using diffractive optical elements for beam homogenization of a 100 J level high-energy Nd:glass green pump laser in a Ti:sapphire final amplifier, we have successfully generated broadband high-energy output with a near-perfect top-hat-like intensity distribution.