| 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 and N. L. PEREIRA. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. CIRCULATION RESEARCH. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS, 2023, vol. 133, No 10, p. 810-825. ISSN 0009-7330. Available from: https://dx.doi.org/10.1161/CIRCRESAHA.123.323200. |
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@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 and N. L. PEREIRA. Myocardial Recovery in Recent Onset Dilated Cardiomyopathy: Role of CDCP1 and Cardiac Fibrosis. \textit{CIRCULATION RESEARCH}. PHILADELPHIA: LIPPINCOTT WILLIAMS \&{} WILKINS, 2023, vol.~133, No~10, p.~810-825. ISSN~0009-7330. Available from: https://dx.doi.org/10.1161/CIRCRESAHA.123.323200.
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