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Show a Coronary Arteries from Mice with Cardiac-Selective Deletion of the Insulin Receptor (CIRKO) are Resistant of Dysfunction Evoked by Pressure-Overload Earl Healy and J- David Symons College of Health and School of Medicine Left-venmcularhyperiiophy e a dm tally relevant problem Tq model 1 h"^ condition in mVea restndcn -Ike.. a'bandH is placedarour>dthe ftOrU M.hl. JnrCic Kin Jiik]| VJlirn lhriL[li»nirkT nf 1 \\r jnrCa"r; ri¦¦:J11¦:¦:¦ iJ ihe leir-'/Hnii Kile h js [o devdop greater ^e^ure taopen rheaonk valve After ^veral weeks or«ccciure co thla "pr«tu le overlc^d" 1he left ¦ventricular will thicken? iflv'hff^rtrophie5'w ir'r|>::'ii ^r-!¦::¦ nnrrrLahvr w;il h'i'niV:-!!. Wr jnL^lixJying Ihr i to pfesaure-ovtHodd in inke wlch L^rUiac-ieleLi rve delei Pin ofihe in-sulln recepcor L-LlRKO]. CIFlKO mice are used 1o mtdei Impal red In- rKeptor mediated sjcj n^l trjnKJu^tKm that ^^ur^m mdivriunh \\\.i\v U'\ Thur; .i cllnl .il P ¦• I ii¦¦ i pi bnjuu1 ¦ i I ilh greacei nikrbi dei/ek?plng ljrUiuVd^i u Ldi li-.-¦¦-- ¦ ^m\ E vniiiurfa AriLrk-H Iiviii MhUWhli t ±iiIdl-. l^i Vr.......nhT P11 k ¦ j-I 111 kfi>LH1 K" I ¦¦ hiki.HI h irl Mr-ife bJ 1 h ¦¦ id \lhp3hi 4 4t»rr Hi llnHta fcn u .i- i Background ¦-* -I-.r.iTft4^_|Hrt^Vr I Tm -LU MypDthc-iis ¦ ¦ ¦ ¦ Hi - r.'r tj Mtthad* Q _ :*J_""?_ : " j7i ^r" ¦^^rti j]: - ¦ Concl JManr. ¦ Summary In a | i i " I ¦ I i^:1 vlKHUfl Chnl r h^arli dn nnl | - i I ¦ | - | I | i i ¦ v "i Ii ¦ n ly <¦¦ 11 >|.il iy I rj-i eKdrnple. heani NurnCIMKO miLe erfii brc dysfuncclon ch^c lichardLieMzed by feft-vencriLUlar dilalBtkifi arvJ reduced Tradlonal shorienlng compared com ce wrth iniact Intulln receptor rnedated signal crain«Jucdon(l*Hw4d Ivpernice"^!. Further, we obwr'ved evidence in the subenctxardiumutf.. the innermost layer of the ifual ill I | ¦ --. ¦ I f hi y. i. \ ¦ ''IMr.ill ' in CIRKH . \ iV" i i ¦ ¦ hty pi | subfirhixandld I fitf oiii in C IkRO nik» ii caused by po« bbad flow tottib area i is'E/unctlon. Sp»^lrKally, we tested che hypothMlt 1 hat tGrcna^ rascular c^E/unctlon It g leacer in mice m ip&pt?n5e 1o ?ortr bandmcj. Fourteen day? aftei pLrrnnn the *srtr band, heart weight^body weq hH ww. ilinilrtr Ix'l wcrn WT\SO^-f/- 1_14| rtiKJC"IRKO\7 76-/-1 ?^| mm\ indicallny llul i ilniiljr^i^qrr^1 nf l sibted between ^roupi br>doihetol v\d vauAr smcoth muade hinctlon then v»e asseied uilrk( laphy Ou r main end-point it vasoreLaxal \on via mechan ismt chai are dependent u pon a Fund cnalencki helium. To wwsithisv^eadmlriiHervantxj? pharrnacologic?! protflsiothe isolated veweUind mtxiHor thedecreaw ir vjv ubr IriiMnn I I ¦ ¦ 11 i ¦ ¦ '/¦¦ I ' crtiKr^ rnctrt h^hum-dqarndrnl vflKnrla^al»n In in 11111 -: p iiiv.kJ1 lSNP| causfiiendochenurn-lndepericfcnt"rasorela^tlon linie-ieiponiecuwtir.o ACh< 1Q-BM-10-5 MldirJSNM.l ^flM lcMO-4 M^were performed on vetsel^ thac were precontracted uilng the 1 h romboKne recepicM mimetic LH&619_ dow responw curve was separated by Jt> mi n We oteervKd 1 hat mwim?l ACh evohed vawrelwation was */-SliilniH^K'liWT-AnrtiidnRKO-ArSniKaK1i|K'cCiwly ThH^rcljU indicaK- IhaC wai arxnllihed In W1-AB rnke. bui remained Intact ki CTflKG-AB mfce Wecbierved ch^c relaxation wat62-M/^ and/H-/-ao^ In veHehWT-ABand ClfiKO-Aftmke, respecthffitv: TJiesedata indrateihatSNP evoked w5oretiM3tionn&in-||l?i t^twepn \\ i^up?. vitnc h ?hov^ that WT AE had int^ri vhik u Uir ¦;maolh rnu'rC k1 Tiiik l»n T.ikdi Id ii i Ihr-^r i^iuhi l> ¦ I Id I hnL c nnLlu-.K^n 11 ¦ ¦ ^^r^iury wi^rlvfr^in CIR<0 /¦¦¦ mk* are niofe resistant g> va^^ular dysfurttfcm after tw& vseka of preanre ovefknd ccfnpared to WT-Afi These, resuhsdldnot tupportdui hypothetic However, these findings do suggest thai ClRKO-AB mice may "upregulale" arx^her enckitheliurn dep^ndeni vawdilator me^han^m feg-endothelium derived hype" p^Uinzinp Factor7!. may VHdrr |
