Myocardial Recovery in Recent Onset Dilated Cardiomyopathy:
Role of CDCP1 and Cardiac Fibrosis

J 2023

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis

LIU, D., M. WANG, V. MURTHY, D. M. MCNAMARA, T. T. L. NGUYEN et. al.

Základní údaje

Originální název

Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis

Autoři

LIU, D., M. WANG, V. MURTHY, D. M. MCNAMARA, T. T. L. NGUYEN, T. J. PHILIPS, H. VYAS, H. GAO, J. SAHNI, R. C. STARLING, L. T. COOPER, M. K. SKIME, A. BATZLER, G. D. JENKINS, S. BARLERA, S. PILEGGI, L. MESTRONI, M. MERLO, G. SINAGRA, F. PINET, Jan KREJČÍ (203 Česká republika, domácí), Anna CHALOUPKA (203 Česká republika, domácí), J. D. MILLER, P. DE GROOTE, D. J. TSCHUMPERLIN, R. M. WEINSHILBOUM a N. L. PEREIRA (garant)

Vydání

CIRCULATION RESEARCH, PHILADELPHIA, LIPPINCOTT WILLIAMS & WILKINS, 2023, 0009-7330

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 20.100 v roce 2022

Kód RIV

RIV/00216224:14110/23:00132227

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1161/CIRCRESAHA.123.323200

UT WoS

001098230800003

Klíčová slova anglicky

cardiomyopathy dilated; fibrosis; genetics; genome-wide association study; heart failure; humansventricular remodeling

Štítky

14110115, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 29. 2. 2024 08:41, Mgr. Tereza Miškechová

Anotace

V originále

BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM.METHODS: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction.RESULTS: The genome-wide association study identified a highly suggestive locus that mapped to the 5 '-flanking region of the CDCP1 (CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435; P=7.12x10-7). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis.CONCLUSIONS: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.

Návaznosti

MUNI/A/1410/2022, interní kód MU

Název: Nové trendy v diagnostice a managementu srdečních onemocnění

Investor: Masarykova univerzita, Nové trendy v diagnostice a managementu srdečních onemocnění

Citovat

LIU, D., M. WANG, V. MURTHY, D. M. MCNAMARA, T. T. L. NGUYEN, T. J. PHILIPS, H. VYAS, H. GAO, J. SAHNI, R. C. STARLING, L. T. COOPER, M. K. SKIME, A. BATZLER, G. D. JENKINS, S. BARLERA, S. PILEGGI, L. MESTRONI, M. MERLO, G. SINAGRA, F. PINET, Jan KREJČÍ, Anna CHALOUPKA, J. D. MILLER, P. DE GROOTE, D. J. TSCHUMPERLIN, R. M. WEINSHILBOUM a N. L. PEREIRA. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. CIRCULATION RESEARCH. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS, 2023, roč. 133, č. 10, s. 810-825. ISSN 0009-7330. Dostupné z: https://dx.doi.org/10.1161/CIRCRESAHA.123.323200.

@article{2338917,
   author = {Liu, D. and Wang, M. and Murthy, V. and McNamara, D. M. and Nguyen, T. T. L. and Philips, T. J. and Vyas, H. and Gao, H. and Sahni, J. and Starling, R. C. and Cooper, L. T. and Skime, M. K. and Batzler, A. and Jenkins, G. D. and Barlera, S. and Pileggi, S. and Mestroni, L. and Merlo, M. and Sinagra, G. and Pinet, F. and Krejčí, Jan and Chaloupka, Anna and Miller, J. D. and de Groote, P. and Tschumperlin, D. J. and Weinshilboum, R. M. and Pereira, N. L.},
   article_location = {PHILADELPHIA},
   article_number = {10},
   doi = {http://dx.doi.org/10.1161/CIRCRESAHA.123.323200},
   keywords = {cardiomyopathy dilated; fibrosis; genetics; genome-wide association study; heart failure; humansventricular remodeling},
   language = {eng},
   issn = {0009-7330},
   journal = {CIRCULATION RESEARCH},
   title = {Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis},
   url = {https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.123.323200},
   volume = {133},
   year = {2023}
}

TY  - JOUR
ID  - 2338917
AU  - Liu, D. - Wang, M. - Murthy, V. - McNamara, D. M. - Nguyen, T. T. L. - Philips, T. J. - Vyas, H. - Gao, H. - Sahni, J. - Starling, R. C. - Cooper, L. T. - Skime, M. K. - Batzler, A. - Jenkins, G. D. - Barlera, S. - Pileggi, S. - Mestroni, L. - Merlo, M. - Sinagra, G. - Pinet, F. - Krejčí, Jan - Chaloupka, Anna - Miller, J. D. - de Groote, P. - Tschumperlin, D. J. - Weinshilboum, R. M. - Pereira, N. L.
PY  - 2023
TI  - Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis
JF  - CIRCULATION RESEARCH
VL  - 133
IS  - 10
SP  - 810-825
EP  - 810-825
PB  - LIPPINCOTT WILLIAMS & WILKINS
SN  - 00097330
KW  - cardiomyopathy dilated
KW  - fibrosis
KW  - genetics
KW  - genome-wide association study
KW  - heart failure
KW  - humansventricular remodeling
UR  - https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.123.323200
N2  - BACKGROUND: Dilated cardiomyopathy (DCM) is a major cause of heart failure and carries a high mortality rate. Myocardial recovery in DCM-related heart failure patients is highly variable, with some patients having little or no response to standard drug therapy. A genome-wide association study may agnostically identify biomarkers and provide novel insight into the biology of myocardial recovery in DCM.METHODS: A genome-wide association study for change in left ventricular ejection fraction was performed in 686 White subjects with recent-onset DCM who received standard pharmacotherapy. Genome-wide association study signals were subsequently functionally validated and studied in relevant cellular models to understand molecular mechanisms that may have contributed to the change in left ventricular ejection fraction.RESULTS: The genome-wide association study identified a highly suggestive locus that mapped to the 5 '-flanking region of the CDCP1 (CUB [complement C1r/C1s, Uegf, and Bmp1] domain containing protein 1) gene (rs6773435; P=7.12x10-7). The variant allele was associated with improved cardiac function and decreased CDCP1 transcription. CDCP1 expression was significantly upregulated in human cardiac fibroblasts (HCFs) in response to the PDGF (platelet-derived growth factor) signaling, and knockdown of CDCP1 significantly repressed HCF proliferation and decreased AKT (protein kinase B) phosphorylation. Transcriptomic profiling after CDCP1 knockdown in HCFs supported the conclusion that CDCP1 regulates HCF proliferation and mitosis. In addition, CDCP1 knockdown in HCFs resulted in significantly decreased expression of soluble ST2 (suppression of tumorigenicity-2), a prognostic biomarker for heart failure and inductor of cardiac fibrosis.CONCLUSIONS: CDCP1 may play an important role in myocardial recovery in recent-onset DCM and mediates its effect primarily by attenuating cardiac fibrosis.
ER  -

LIU, D., M. WANG, V. MURTHY, D. M. MCNAMARA, T. T. L. NGUYEN, T. J. PHILIPS, H. VYAS, H. GAO, J. SAHNI, R. C. STARLING, L. T. COOPER, M. K. SKIME, A. BATZLER, G. D. JENKINS, S. BARLERA, S. PILEGGI, L. MESTRONI, M. MERLO, G. SINAGRA, F. PINET, Jan KREJČÍ, Anna CHALOUPKA, J. D. MILLER, P. DE GROOTE, D. J. TSCHUMPERLIN, R. M. WEINSHILBOUM a N. L. PEREIRA. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. \textit{CIRCULATION RESEARCH}. PHILADELPHIA: LIPPINCOTT WILLIAMS \&{} WILKINS, 2023, roč.~133, č.~10, s.~810-825. ISSN~0009-7330. Dostupné z: https://dx.doi.org/10.1161/CIRCRESAHA.123.323200.

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