Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload / Filomena M.C.; Yamamoto D.L.; Carullo P.; Medvedev R.; Ghisleni A.; Piroddi N.; Scellini B.; Crispino R.; D'autilia F.; Zhang J.; Felicetta A.; Nemska S.; Serio S.; Tesi C.; Catalucci D.; Linke W.A.; Polishchuk R.; Poggesi C.; Gautel M.; Bang M.-L.. - In: ELIFE. - ISSN 2050-084X. - ELETTRONICO. - 10:(2021), pp. e58313-e58313. [10.7554/eLife.58313]

Myopalladin knockout mice develop cardiac dilation and show a maladaptive response to mechanical pressure overload

Piroddi N.;Scellini B.;Zhang J.;Serio S.;Tesi C.;Poggesi C.;
2021

Abstract

Myopalladin (MYPN) is a striated muscle-specific immunoglobulin domain-containing protein located in the sarcomeric Z-line and I-band. MYPN gene mutations are causative for dilated (DCM), hypertrophic and restrictive cardiomyopathy. In a yeast two-hybrid screening, MYPN was found to bind to titin in the Z-line, which was confirmed by microscale thermophoresis. Cardiac analyses of MYPN knockout (MKO) mice showed the development of mild cardiac dilation and systolic dysfunction, associated with decreased myofibrillar isometric tension generation and increased resting tension at longer sarcomere lengths. MKO mice exhibited a normal hypertrophic response to transaortic constriction (TAC), but rapidly developed severe cardiac dilation and systolic dysfunction, associated with fibrosis, increased fetal gene expression, higher intercalated disc fold amplitude, decreased calsequestrin-2 protein levels, and increased desmoplakin and SORBS2 protein levels. Cardiomyocyte analyses showed delayed Ca2+ release and reuptake in unstressed MKO mice as well as reduced Ca2+ spark amplitude post-TAC, suggesting that altered Ca2+ handling may contribute to the development of DCM in MKO mice.
2021
10
e58313
e58313
Goal 3: Good health and well-being for people
Filomena M.C.; Yamamoto D.L.; Carullo P.; Medvedev R.; Ghisleni A.; Piroddi N.; Scellini B.; Crispino R.; D'autilia F.; Zhang J.; Felicetta A.; Nemska...espandi
File in questo prodotto:
File Dimensione Formato  
elife-58313-v2.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 10.43 MB
Formato Adobe PDF
10.43 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1247467
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 11
  • ???jsp.display-item.citation.isi??? 12
social impact