Naslov
Mitohondrijska kontrola kvalitete u zatajivanju srca
(Mitochondrial Quality Control in Failing Human Hearts)

Autori
Svaguša, Tomo ; Sikirić, Sunčana ; Milavić, Marija ; Šepac, Ana ; Seiwerth, Sven ; Miličić, Davor ; Gasparović, Hrvoje ; Biočina, Bojan ; Rudež, Igor ; Sutlić Željko ; Manola, Šime ; Varvodić, Josip ; Udovičić, Mario ; Urlić Marjan ; Ivanković, Stjepan ; Pleština, Stjepko ; Paić Frane ; Kulić, Ana ; Baković, Petra ; Sedlić, Filip

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
14. kongres Hrvatskog kardiološkog društva

Mjesto i datum
Zagreb, Hrvatska, 24.11.2022. - 27.11.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
zatajivanje srca ; dilatativna kardiomiopatija ; ishemijska kardiomiopatija ; kvaliteta kontrole mitohondrija ; UPRmt, mitofagija ; translokaze unutarnje membrane, fuzija, fisija
(heart failure, dilated cardiomyopathy, ischemic cardiomyopathy, mitochondrial quality control, UPRmt, mitophagy, translocases of the inner membrane, fusion, fission)

Sažetak
Aims. Mitochondrial dysfunction is one of the key factors underlying heart failure in patients. We performed a comprehensive analysis of expression of genes crucial for the mitochondrial quality control (MQC), including mitochondrial unfolded protein response (UPRmt), mitophagy, translocases of the inner membrane (TIM), fusion-fission balance and mitochondrial biogenesis. In addition, protein expression of selected UPRmt genes was also determined. Metods and Results. Real-time PCR was used to quantify the expression of 43 MQC genes in human myocardial samples of ischemic (ICM)- and dilated cardiomyopathy (DCM)-induced heart failure (HF) and control myocardial samples. Protein expression was quantified by ELISA. The following genes were downregulated in failing hearts ischemic and dilated cardiomyopathy: COX1, SIRT1, MTOR, MFF, DDIT3, UBL5, HSPA9, HSPE1, YME1L, LONP1, SPG7, HTRA2, OMA1, TIMM23, TIMM17A, TIMM17B, TIMM44, PAM16, TIMM22, TIMM9, TIMM10, PINK1, PARK2, ROTH1, PARL, FUNDC1, BNIP3, BNIP3L, TPCN2, LAMP2, MAP1LC3A and, BECN1. Moreover, MFN2, EIF2AK4 and ULK1 were downregulated in heart failure from dilated, but not ischemic cardiomyopathy. Only JUN was significantly different between ischemic and dilated cardiomyopathy. PPARGC1, OPA1, JUN, CEBPB, EIF2A, HSPD1, TIMM50 and TPCN1 were not significantly different between control and any form of heart failure. UPRmt proteins CLPP, LONP1, OMA1, SPG7 and HSP10 were downregulated in both ICM and DCM. Conclusions. Human ischemic- and dilated cardiomyopathy-induced heart failure is associated with the downregulation of multiple genes and proteins involved in UPRmt, mitophagy, TIM complexes and fusion-fission balance. This indicates severe impairment of MQC in failing human hearts.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti

POVEZANOST RADA