Portal de Periódicos da CAPES

Angiotensin II-mediated up-regulation of connective tissue growth factor promotes atrial tissue fibrosis in the canine atrial fibrillation model

2012; Oxford University Press; Volume: 14; Issue: 8 Linguagem: Inglês

10.1093/europace/eus052

1532-2092

Michiro Kiryu, Shinichi Niwano, Hiroe Niwano, Jun Kishihara, Yuki Aoyama, Hidehira Fukaya, Y Masaki, T. Izumi,

Periodontal Regeneration and Treatments

Remodelling of the extracellular matrix (ECM) plays an important role in the production of arrhythmogenic substrate for atrial fibrillation (AF), and is considered to be promoted by the connective tissue growth factor (CTGF).Our objective was to assess the relationship between CTGF and ECM synthesis, and the effect of olmesartan on these processes. Methods and resultsFifteen canine AF models were produced by rapid atrial stimulation.They were divided into three groups: pacing control (n ¼ 5): 6-week pacing, pacing + olmesartan (n ¼ 5): pacing with olmesartan (2 mg/kg/day), and nonpacing group (n ¼ 5).In the pacing control group, messenger ribonucleic acid expressions of CTGF and collagen types 1 and 3 were up-regulated in comparison with the non-pacing group (P , 0.05) while transforming growth factor-b (TGF-b) did not exhibit a significant difference.In the pacing + olmesartan group, these up-regulations were suppressed (P , 0.05).In fluorescent immunostaining, the expression of CTGF was localized in the cytoplasm.The protein level of collagen type 3 was increased in the pacing control and it was suppressed in the pacing + olmesartan group. ConclusionsCTGF and associated genes were up-regulated in the atria with the appearance of fibrosis.Because this up-regulation was independent of TGF-b and suppressed by olmesartan, CTGF up-regulation was considered to be mediated by angiotensin II.