RESUMO
Vasostatin 1 (VS-1) plays an important role in the regulation of various tissue injury and repair processes, but its role in aortic aneurysm remains unclear. The plasmid-like nanoparticles containing the vasostatin-1 gene Pul-PGEA-pCas-sgVs-1 were constructed, and their guarantee, safety, hemolysis, and particle size were analyzed. Eighty-four eight-week-old male ApoE-mice were randomly divided into blank group (without any treatment), model group (Ang II aortic aneurysm model + tail injection of PBS), control group (modeling + tail injection of Pul-PGEA-pCas9), and experimental group (modeling + tail injection of Pul-PGEA-pCas-sgVs-1), with 21 rats in each group. The incidence, mortality, and maximum diameter of abdominal aortic aneurysm (AAA) and the contents of high sensitivity C-reactive protein (HS-CRP), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), and TNF-a in serum were compared in different groups of mice. The results showed that Pul-PGEA-pCas-sgVs-1 had good biosafety and transfection ability. The maximum diameter of abdominal aorta, incidence of abdominal aortic aneurysm, mortality, and the expression levels of HS-CRP, ICAM-1, VCAM-1, and TNF-a in the experimental group were lower than those in the model group (P< 0.05). These results indicated that the plasmid-like nanoparticles Pul-PGEA-pCas-sgVs-1 can inhibit the development of aorta by down-regulating the expression of inflammatory factors, which played a good protective role on the aorta.
Assuntos
Aneurisma da Aorta Abdominal , Cromogranina A , Regulação da Expressão Gênica , Nanopartículas , Fragmentos de Peptídeos , Plasmídeos , Animais , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/prevenção & controle , Cromogranina A/biossíntese , Cromogranina A/genética , Modelos Animais de Doenças , Masculino , Camundongos , Camundongos Knockout para ApoE , Nanopartículas/química , Nanopartículas/uso terapêutico , Fragmentos de Peptídeos/biossíntese , Fragmentos de Peptídeos/genética , Plasmídeos/química , Plasmídeos/genética , Plasmídeos/farmacologiaRESUMO
The effects of transfection of N-terminal fragment of chromogranin A Vasostatin-1 (VS-1) nanocarriers on formation of abdominal aortic aneurysm (AAA) were discussed, and its mechanism was analyzed. Nanoparticles containing VS-1 genes were prepared by emulsion solvent evaporation method, and property of nanoparticles was examined. A total of 30 male SD rats were divided randomly into sham group (normal saline), AAA group (Type I porcine pancreatic elastase), and VS-1 group (Type I porcine pancreatic elastase+VS-1 suspension liquid). The diameter dilation of rats was measured, abdominal aortic morphology was observed by HE staining, and levels of AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were examined by immunohistochemistry and Western blot. Correlation between AMPK as well as mTOR and diameter dilation was analyzed by Pearson correlation. VS-1 genes in VS-1 nanoparticles were 4.51% and coating efficiency of genes was 88%. Compared with rats in sham group, diameter dilation of rats in AAA group increased, damage of abdominal aorta in rats was obvious, p-AMPK decreased, and p-mTOR increased in AAA group. Compared with AAA group, diameter dilation of rats in VS-1 group decreased, abdominal aorta of rats was improved, p-AMPK increased, and p-mTOR decreased. The comparison of all above indicators had statistical meaning (P < 0.05). p-AMPK and p-mTOR were negatively (r = -0.9150 and P = 0.006) and positively correlated with the diameter dilation (r = -0.9206 and P = 0.001). VS-1 nanoparticles could inhibit the formation of AAA, which might be related to the activation of AMPK/mTOR signal path.