ec855489d5544d1154160cacddba0d45 241233.pdf 5eb8918c521690619999db9d20eca5f5a4af1d50 241233.pdf c50c49372d1b4c249c51831b7bfe437133c314df33091e6a97b28369cedd40cc 241233.pdf Title: Connexin 43 Deficiency Is Associated with Reduced Myocardial Scar Size and Attenuated TGF1 Signaling after Transient Coronary Occlusion in Conditional Knock-Out Mice Subject: Previous studies demonstrated a reduction in myocardial scar size in heterozygous Cx43+/- mice subjected to permanent coronary occlusion. However, patients presenting with ST segment elevation myocardial infarction often undergo rapid coronary revascularization leading to prompt restoration of coronary flow. Therefore, we aimed to assess changes in scar size and left ventricular remodeling following transient myocardial ischemia (45 min) followed by 14 days of reperfusion using Cx43fl/fl (controls) and Cx43Cre-ER(T)/fl inducible knock-out (Cx43 content: 50%) mice treated with vehicle or 4-hydroxytamoxifen (4-OHT) to induce a Cre-ER(T)-mediated global deletion of the Cx43 floxed allele. The scar area (picrosirius red), measured 14 days after transient coronary occlusion, was similarly reduced in both vehicle and 4-OHT-treated Cx43Cre-ER(T)/fl mice, compared to Cx43fl/fl animals, having normal Cx43 levels (15.78% 3.42% and 16.54% 2.31% vs. 25.40% 3.14% and 22.43% 3.88% in vehicle and 4-OHT-treated mice, respectively, p = 0.027). Left ventricular dilatation was significantly attenuated in both Cx43-deficient groups (p = 0.037 for left ventricular end-diastolic diameter). These protective effects were correlated with an attenuated enhancement in pro-transforming growth factor beta 1 (TGF1) expression after reperfusion. In conclusion, our data demonstrate that Cx43 deficiency induces a protective effect on scar formation after transient coronary occlusion in mice, an effect associated with reduced left ventricular remodeling and attenuated enhancement in pro-TGF1 expression. Keywords: connexin 43; left ventricular remodeling; collagen; ischemia–reperfusion; myocardial infarct Author: Laura Valls-Lacalle, Marta Consegal, Marisol Ruiz-Meana, Begoña Benito, Javier Inserte, Ignasi Barba, Ignacio Ferreira-González and Antonio Rodríguez-Sinovas Creator: LaTeX with hyperref package Producer: pdfTeX-1.40.18 CreationDate: Thu Apr 23 13:03:23 2020 CEST ModDate: Thu Apr 23 13:03:23 2020 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 10 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2087536 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- DXQJKD+URWPalladioL-Ital Type 1 Custom yes yes no 85 0 PIBMDC+URWPalladioL-Bold Type 1 Custom yes yes no 86 0 ZYYJXI+EURB10 Type 1 Builtin yes yes no 87 0 SSNIUI+VnURWPalladioL-Bold Type 1 Custom yes yes no 88 0 ZBGBEV+URWPalladioL-Roma Type 1 Custom 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HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: ぉのぴひはつふっぴどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸲ Item: Title: きちぴづひどちぬびぜ〴ぜ〰ちのつぜ〴ぜ〰きづぴとはつびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぁのどねちぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぅへばづひどねづのぴちぬぜ〴ぜ〰ぐひはぴはっはぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ごひちのびぴとはひちっどっぜ〴ぜ〰ぅっとはっちひつどはでひちばとべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Children: Item: Title: ぁのどねちぬびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㈩‾㸊⡜㌷㙜㌷㝜〰ぅへばづひどねづのぴちぬぜ〴ぜ〰ぐひはぴはっはぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ごひちのびぴとはひちっどっぜ〴ぜ〰ぅっとはっちひつどはでひちばとべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ぅへばづひどねづのぴちぬぜ〴ぜ〰ぐひはぴはっはぬぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㌩‾㸊⡜㌷㙜㌷㝜〰きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ごひちのびぴとはひちっどっぜ〴ぜ〰ぅっとはっちひつどはでひちばとべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㐩‾㸊⡜㌷㙜㌷㝜〰ごひちのびぴとはひちっどっぜ〴ぜ〰ぅっとはっちひつどはでひちばとべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: ごひちのびぴとはひちっどっぜ〴ぜ〰ぅっとはっちひつどはでひちばとべぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㔩‾㸊⡜㌷㙜㌷㝜〰しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: しづびぴづひのぜ〴ぜ〰あぬはぴぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㈮㘩‾㸊⡜㌷㙜㌷㝜〰こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: こぴちぴどびぴどっびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸳ Item: Title: げづびふぬぴびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮ㄩ‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぃへ〴〳ぜ〴ぜ〰いづてどっどづのっべぜ〴ぜ〰はのぜ〴ぜ〰きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぃへ〴〳ぜ〴ぜ〰いづてどっどづのっべぜ〴ぜ〰はのぜ〴ぜ〰ぐはびぴ〭ぉのてちひぴどはのぜ〴ぜ〰がづてぴぜ〴ぜ〰ざづのぴひどっふぬちひぜ〴ぜ〰げづねはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぃとちのでづびぜ〴ぜ〰どのぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰こづぬづっぴづつぜ〴ぜ〰うどぢひはぴどっぜ〴ぜ〰ちのつぜ〴ぜ〰げづねはつづぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰〱〴ぜ〴ぜ〰いちべびぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Children: Item: Title: ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぃへ〴〳ぜ〴ぜ〰いづてどっどづのっべぜ〴ぜ〰はのぜ〴ぜ〰きべはっちひつどちぬぜ〴ぜ〰こっちひぜ〴ぜ〰こどぺづぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㈩‾㸊⡜㌷㙜㌷㝜〰ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぃへ〴〳ぜ〴ぜ〰いづてどっどづのっべぜ〴ぜ〰はのぜ〴ぜ〰ぐはびぴ〭ぉのてちひぴどはのぜ〴ぜ〰がづてぴぜ〴ぜ〰ざづのぴひどっふぬちひぜ〴ぜ〰げづねはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぃとちのでづびぜ〴ぜ〰どのぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰こづぬづっぴづつぜ〴ぜ〰うどぢひはぴどっぜ〴ぜ〰ちのつぜ〴ぜ〰げづねはつづぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰〱〴ぜ〴ぜ〰いちべびぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぅててづっぴびぜ〴ぜ〰はてぜ〴ぜ〰ぃへ〴〳ぜ〴ぜ〰いづてどっどづのっべぜ〴ぜ〰はのぜ〴ぜ〰ぐはびぴ〭ぉのてちひぴどはのぜ〴ぜ〰がづてぴぜ〴ぜ〰ざづのぴひどっふぬちひぜ〴ぜ〰げづねはつづぬどのでぜ〴〩਼㰠⽓ 䝯呯 䐠⡳畢獥捴楯渮㌮㌩‾㸊⡜㌷㙜㌷㝜〰ぃとちのでづびぜ〴ぜ〰どのぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰こづぬづっぴづつぜ〴ぜ〰うどぢひはぴどっぜ〴ぜ〰ちのつぜ〴ぜ〰げづねはつづぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰〱〴ぜ〴ぜ〰いちべびぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: ぃとちのでづびぜ〴ぜ〰どのぜ〴ぜ〰ぅへばひづびびどはのぜ〴ぜ〰はてぜ〴ぜ〰こづぬづっぴづつぜ〴ぜ〰うどぢひはぴどっぜ〴ぜ〰ちのつぜ〴ぜ〰げづねはつづぬどのでぜ〴ぜ〰きちひにづひびぜ〴ぜ〰〱〴ぜ〴ぜ〰いちべびぜ〴ぜ〰ちてぴづひぜ〴ぜ〰ごひちのびどづのぴぜ〴ぜ〰ぃはひはのちひべぜ〴ぜ〰くっっぬふびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸴ Item: Title: いどびっふびびどはのぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: ぃはのっぬふびどはのびぜ〴〩਼㰠⽓ 䝯呯 䐠⡳散瑩潮⸵ Item: Title: げづてづひづのっづび Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: GBLQZB+Rpxi FontSubset: true FirstChar: 11 LastChar: 11 FontDescriptor: FontName: GBLQZB+Rpxi Flags: Symbolic FontBBox: -162, -280, 856, 733 FontFile: true Font: BaseFont: DXQJKD+URWPalladioL-Ital FontSubset: true FirstChar: 2 LastChar: 122 FontDescriptor: FontName: DXQJKD+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true 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Subtype: Link Rect: 234, 202, 407, 213 Checksum: 9f9cbe11 Type: CRC32 Checksum: ec855489d5544d1154160cacddba0d45 Type: MD5 Checksum: 5eb8918c521690619999db9d20eca5f5a4af1d50 Type: SHA-1