OdysseusBot: Новая страница: «Adenylyl cyclase-associated protein 2 (CAP 2) ==Publications== {{medline-entry |title=Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays...»

2021-05-12T15:08:03Z

Новая страница: «Adenylyl cyclase-associated protein 2 (CAP 2) ==Publications== {{medline-entry |title=Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays...»

Новая страница

Adenylyl cyclase-associated protein 2 (CAP 2)

==Publications==

{{medline-entry
|title=Targeting MRTF/[[SRF]] in [[CAP2]]-dependent dilated cardiomyopathy delays disease onset.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30762586
|abstract=About one-third of dilated cardiomyopathy (DCM) cases are caused by mutations in sarcomere or cytoskeletal proteins. However, treating the cytoskeleton directly is not possible because drugs that bind to actin are not well tolerated. Mutations in the actin binding protein [[CAP2]] can cause DCM and KO mice, either whole body ([[CAP2]]-KO) or cardiomyocyte-specific KOs ([[CAP2]]-CKO) develop DCM with cardiac conduction disease. RNA sequencing analysis of [[CAP2]]-KO hearts and isolated cardiomyocytes revealed overactivation of fetal genes, including serum response factor-regulated ([[SRF]]-regulated) genes such as Myl9 and Acta2 prior to the emergence of cardiac disease. To test if we could treat [[CAP2]]-KO mice, we synthesized and tested the [[SRF]] inhibitor CCG-1423-8u. CCG-1423-8u reduced expression of the [[SRF]] targets Myl9 and Acta2, as well as the biomarker of heart failure, Nppa. The median survival of [[CAP2]]-CKO mice was 98 days, while CCG-1423-8u-treated CKO mice survived for 116 days and also maintained normal cardiac function longer. These results suggest that some forms of sudden cardiac death and cardiac conduction disease are under cytoskeletal stress and that inhibiting signaling through [[SRF]] may benefit DCM by reducing cytoskeletal stress.
|mesh-terms=* Anilides
* Animals
* Benzamides
* Cardiomyopathy, Dilated
* Carrier Proteins
* Cytoskeleton
* Disease Models, Animal
* Female
* Fetus
* Gene Expression Regulation, Developmental
* Heart
* Humans
* Longevity
* Male
* Mice
* Myocardium
* Myocytes, Cardiac
* RNA-Seq
* Serum Response Factor
* Signal Transduction
* Time Factors
* Transcription Factors
|keywords=* Cardiology
* Therapeutics
* Transcription
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483011
}}

CAP2 - История изменений

OdysseusBot: Новая страница: «Adenylyl cyclase-associated protein 2 (CAP 2) ==Publications== {{medline-entry |title=Targeting MRTF/SRF in CAP2-dependent dilated cardiomyopathy delays...»