title: Dynamic alterations of connexin43, matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 during ventricular fibrillation in canine.
abstract: The aim of this study is to investigate the dynamic alterations of cardiac connexin 43 (Cx43), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the setting of different ventricular fibrillation (VF) duration. In this study, thirty-two dogs were randomly divided into sham control group, 8-min VF group, 12-min VF group, and 30-min VF group. Cx43 and phosphorylated Cx43 (p-Cx43) in tissues were detected by western blot and immunofluorescence analysis. MMP-2 and TIMP-2 were detected by western blot and immunohistochemistry analysis. The results showed that Cx43 levels in three VF groups were significantly decreased compared with sham control group. p-Cx43 levels in 12-min and 30-min VF groups were significantly reduced compared with sham control group. The ratio of p-Cx43/Cx43 was also decreased in VF groups. Compared with sham controls, no significant difference was observed between the sham control group and 8-min VF group in MMP-2 level, but MMP-2 level increased in 12-min and 30-min VF groups. The ratios of MMP-2/TIMP-2 were higher in VF groups, and were correlated with the duration of VF. A remarkable correlation was observed between the ratio of p-Cx43/Cx43 and MMP-2/TIMP-2 (r = -0.93, P < 0.01). In conclusion, the alteration of Cx43 and/or p-Cx43 levels and the imbalance of MMP-2 and TIMP-2 may contribute to the initiation and/or persistence of VF. Maneuvers managed to modulate Cx43 level or normalize the balance of MMP-2/TIMP-2 are promising to ameliorate prognosis of VF.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Jinan, 250012, Shandong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Jing-sha
authors.initials: JS
authors.lastname: Li
authors.forename: Hong-zhen
authors.initials: HZ
authors.lastname: Liu
authors.forename: Shao-lei
authors.initials: SL
authors.lastname: Yi
authors.forename: Guo-ying
authors.initials: GY
authors.lastname: Su
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing-quan
authors.initials: JQ
authors.lastname: Zhong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D005455:Fluorescent Antibody Technique; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D010766:Phosphorylation; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism*; D014693:Ventricular Fibrillation / Q000201:enzymology*
chemical_list: D018031:Connexin 43; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2