期刊
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
卷 9, 期 3, 页码 158-167出版社
WILEY
DOI: 10.1111/cts.12393
关键词
-
资金
- National Institutes of Health [MSTP/T32/65841, NCATS/TL1/TR000137, OD007015-01]
- Todd and Karen Wanek Family Program for Hypoplastic Left Heart Syndrome
- Regenerative Medicine Minnesota
- Mayo Clinic Center for Regenerative Medicine [MRM/2015/GSCH/003]
For inherited cardiomyopathies, abnormal sensitivity to intracellular calcium (Ca2+), incurred from genetic mutations, initiates subsequent molecular events leading to pathological remodeling. Here, we characterized the effect of -adrenergic stress in familial dilated cardiomyopathy (DCM) using human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) from a patient with RBM20 DCM. Our findings suggest that -adrenergic stimulation accelerated defective Ca2+ homeostasis, apoptotic changes, and sarcomeric disarray in familial DCM hiPSC-CMs. Furthermore, pharmacological modulation of abnormal Ca2+ handling by pretreatment with -blocker, carvedilol, or Ca2+-channel blocker, verapamil, significantly decreased the area under curve, reduced percentage of disorganized cells, and decreased terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic loci in familial DCM hiPSC-CMs after -adrenergic stimulation. These translational data provide patient-based in vitro analysis of -adrenergic stress in RBM20-deficient familial DCM hiPSC-CMs and evaluation of therapeutic interventions to modify heart disease progression, which may be personalized, but more importantly generalized in the clinic.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据