title: Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells.
abstract: Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, China. Electronic address: cf970422@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Nanchang University, Nanchang 330006, China.
authors.forename: ZhenDong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Vascular Surgery, The Second Affiliated Hospital, Nanchang University, Nanchang 330006, China.
authors.forename: XianHua
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology / Q000627:therapeutic use*; D001012:Aorta, Abdominal / Q000000981:diagnostic imaging / Q000503:physiopathology; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D003131:Combined Modality Therapy; D006801:Humans; D007963:Leukocytes, Mononuclear; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008249:Protein-Lysine 6-Oxidase / Q000235:genetics* / Q000378:metabolism; D011817:Rabbits; D033581:Stem Cell Transplantation; D013234:Stem Cells; D014463:Ultrasonography
chemical_list: D000873:Anthracenes; D047428:Protein Kinase Inhibitors; C432165:pyrazolanthrone; D008249:Protein-Lysine 6-Oxidase
keywords: Abdominal aortic aneurysm; C-Jun N-terminal protein kinase; Drug delivery system; SP600125; SP600125 (PubChem CID: 8515); Smooth muscle progenitor cell