{"id":6432,"date":"2023-02-17T06:49:07","date_gmt":"2023-02-17T06:49:07","guid":{"rendered":"https:\/\/beta.nanion.de\/resource_library\/2020-metformin-therapy-confers-cardioprotection-against-the-remodeling-of-gap-junction-in-tachycardia-induced-atrial-fibrillation-dog-model\/"},"modified":"2023-02-17T06:49:08","modified_gmt":"2023-02-17T06:49:08","slug":"2020-metformin-therapy-confers-cardioprotection-against-the-remodeling-of-gap-junction-in-tachycardia-induced-atrial-fibrillation-dog-model","status":"publish","type":"resource_library","link":"https:\/\/nanion.com\/ja\/resource_library\/2020-metformin-therapy-confers-cardioprotection-against-the-remodeling-of-gap-junction-in-tachycardia-induced-atrial-fibrillation-dog-model\/","title":{"rendered":"2020 &#8211; Metformin therapy confers cardioprotection against the remodeling of gap junction in tachycardia-induced atrial fibrillation dog model"},"content":{"rendered":"<p>OBJECTIVE: Metformin, introduced in 1957, is widely used as an anti-diabetic drug and has considerable benefits in cardiovascular disease reportedly, dependent or independent on its glucose-lowering effects. Aim of this study was to investigate the effect of metformin on gap junction and the inducibility of AF. METHODS: Beagle dogs were subjected to acute or chronic pacing at right atrial appendage by a pacemaker to develop an AF model and electrophysiological parameters were measured. In vitro study, a cell fast pacing model was developed by CardioExcyte 96. We performed Western blot, histology immunohistochemical staining and electron microscopy to detect the effect of metformin. RESULTS: In chronic AF model, the inducibility and duration of AF increased obviously after pacing for 6\u202fweeks compared with sham-operated group (Inducibility, 3.33\u202f\u00b1\u202f5.77 vs. 85.33\u202f\u00b1\u202f7.89%, P<0.0001; Duration, 0.8\u202f\u00b1\u202f0.84 vs. 11\u202f\u00b1\u202f2.67\u202fms, P<0.0001). Effective refractory periods (ERP) decreased at left and right left atrium and atrial appendages compared with sham-operated group (123.95\u202f\u00b1\u202f6.57 vs. 89.96\u202f\u00b1\u202f7.39\u202fms P<0.0001). Metformin attenuated the pacing-induced increase in EPR (89.96\u202f\u00b1\u202f7.39 vs. 105.83\u202f\u00b1\u202f7.45\u202fms, P<0.05), AF inducibility and AF duration (Inducibility, 85.33\u202f\u00b1\u202f7.89 vs. 64.17\u202f\u00b1\u202f7.36%, Duration, 11\u202f\u00b1\u202f2.67 vs. 8.62\u202f\u00b1\u202f1.15\u202fms, P<0.05). The expression of Cx43 shows a significant downregulation(about 38%, P<0.001) after chronic pacing and treating with metformin could alleviate this decrease(P<0.01). However, the effect of metformin in acute pacing model is limited. The immunohistochemical staining of cardiac tissue also shown that there is more lateralized Cx43 under pacing condition (87.67\u202f\u00b1\u202f2.52 vs. 60.8\u202f\u00b1\u202f9.13%, P<0.005). These pacing-induced lateralize Cx43 could be alleviated by the metformin (48.4\u202f\u00b1\u202f8.62 vs. 60.8\u202f\u00b1\u202f9.13%, P<0.05). Additionally, metformin could affect the interactions of ZO-1 with p-Src\/Cx43 via decrease the abnormal cAMP level after pacing (84.04\u202f\u00b1\u202f4.58 vs. 69.34\u202f\u00b1\u202f4.5\u202fnmol\/L, P<0.001). CONCLUSIONS:Metformin could alleviate the vulnerability of AF and attenuate the downregulation of gap junction under pacing condition via AMPK pathway and decreasing the P-Src level.\n<\/p>\n","protected":false},"featured_media":0,"template":"","products_tags":[34],"resource_type":[75],"application_areas":[77],"therapeutic_areas":[54],"target_categories":[341],"target_families":[342],"targets":[243],"resource_keyword":[],"class_list":["post-6432","resource_library","type-resource_library","status-publish","hentry","products_tags-cardioexcyte-96","resource_type-publication","application_areas-cell-ipscs-profiling","therapeutic_areas-cardiac-safety-cipa","target_categories-pores-and-toxins","target_families-connexins","targets-cx43"],"acf":[],"_links":{"self":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library\/6432","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_library"}],"about":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/types\/resource_library"}],"wp:attachment":[{"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/media?parent=6432"}],"wp:term":[{"taxonomy":"products_tags","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/products_tags?post=6432"},{"taxonomy":"resource_type","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_type?post=6432"},{"taxonomy":"application_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/application_areas?post=6432"},{"taxonomy":"therapeutic_areas","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/therapeutic_areas?post=6432"},{"taxonomy":"target_categories","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_categories?post=6432"},{"taxonomy":"target_families","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/target_families?post=6432"},{"taxonomy":"targets","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/targets?post=6432"},{"taxonomy":"resource_keyword","embeddable":true,"href":"https:\/\/nanion.com\/ja\/wp-json\/wp\/v2\/resource_keyword?post=6432"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}