BRG1 is a biomarker of hypertrophic cardiomyopathy in human heart specimens

被引:4
作者
Scherba, Jacob C. [1 ]
Halushka, Marc K. [2 ]
Andersen, Nicholas D. [3 ]
Maleszewski, Joseph J. [4 ]
Landstrom, Andrew P. [5 ]
Bursac, Nenad [1 ]
Glass, Carolyn [6 ]
机构
[1] Duke Univ, Dept Biomed Engn, Durham, NC 27710 USA
[2] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA
[3] Duke Univ, Div Cardiovasc & Thorac Surg, Dept Surg, Med Ctr, Durham, NC 27710 USA
[4] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA
[5] Duke Univ, Div Pediat Cardiol, Dept Pediat, Med Ctr, Durham, NC 27710 USA
[6] Duke Univ, Dept Pathol, Med Ctr, 217AM Davison Bldg,40 Duke Med Circle,POB 3712 DU, Durham, NC 27710 USA
关键词
EUROPEAN-SOCIETY; MANAGEMENT; HISTOPATHOLOGY; CARDIOLOGY; DISEASE;
D O I
10.1038/s41598-022-11829-x
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hypertrophic cardiomyopathy (HCM) is a genetic disease of the sarcomere that causes otherwise unexplained cardiac hypertrophy and is associated with sudden death. While previous studies showed the role of the epigenetic modifier Brg1 in mouse models of HCM, additional work is needed to identify its role in humans. We tested the hypothesis that BRG1 expression is increased in periods of cardiac remodeling during fetal growth and in development of HCM. We employed immunohistochemical staining to evaluate protein expression of BRG1 in 796 human cardiac specimens (81 from patients with HCM) and describe elevated BRG1 expression in human fetal hearts in early development. In addition, we not only demonstrate increased expression of BRG1 in HCM, but we also show that other diseases that lead to heart failure have similar BRG1 expression to healthy controls. Inhibition of BRG1 in human induced pluripotent stem cell-derived cardiomyocytes significantly decreases MYH7 and increases MYH6, suggesting a regulatory role for BRG1 in the pathological imbalance of the two myosin heavy chain isoforms in human HCM. These data are the first demonstration of BRG1 as a specific biomarker for human HCM and provide foundation for future studies of epigenetics in human cardiac disease.
引用
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页数:7
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