Mullen McKay, Zhang Angela, Lui George K, Romfh Anitra W, Rhee June-Wha, Wu Joseph C
Stanford Cardiovascular Institute, Stanford University, Stanford, CA, United States.
Department of Physiology, Morehouse School of Medicine, Atlanta, GA, United States.
Front Cardiovasc Med. 2021 Feb 17;8:635280. doi: 10.3389/fcvm.2021.635280. eCollection 2021.
Congenital heart disease (CHD) is a multifaceted cardiovascular anomaly that occurs when there are structural abnormalities in the heart before birth. Although various risk factors are known to influence the development of this disease, a full comprehension of the etiology and treatment for different patient populations remains elusive. For instance, racial minorities are disproportionally affected by this disease and typically have worse prognosis, possibly due to environmental and genetic disparities. Although research into CHD has highlighted a wide range of causal factors, the reasons for these differences seen in different patient populations are not fully known. Cardiovascular disease modeling using induced pluripotent stem cells (iPSCs) is a novel approach for investigating possible genetic variants in CHD that may be race specific, making it a valuable tool to help solve the mystery of higher incidence and mortality rates among minorities. Herein, we first review the prevalence, risk factors, and genetics of CHD and then discuss the use of iPSCs, omics, and machine learning technologies to investigate the etiology of CHD and its connection to racial disparities. We also explore the translational potential of iPSC-based disease modeling combined with genome editing and high throughput drug screening platforms.
先天性心脏病(CHD)是一种多方面的心血管异常疾病,它在出生前心脏就存在结构异常时发生。尽管已知多种风险因素会影响这种疾病的发展,但对于不同患者群体的病因和治疗方法仍缺乏全面的理解。例如,少数族裔受这种疾病的影响尤为严重,且通常预后较差,这可能是由于环境和基因差异所致。尽管对先天性心脏病的研究已经突出了广泛的因果因素,但不同患者群体中出现这些差异的原因尚不完全清楚。利用诱导多能干细胞(iPSC)进行心血管疾病建模是一种研究先天性心脏病中可能存在的种族特异性基因变异的新方法,使其成为帮助解开少数族裔中高发病率和高死亡率之谜的有价值工具。在此,我们首先回顾先天性心脏病的患病率、风险因素和遗传学,然后讨论利用诱导多能干细胞、组学和机器学习技术来研究先天性心脏病的病因及其与种族差异的关系。我们还探讨了基于诱导多能干细胞的疾病建模与基因组编辑和高通量药物筛选平台相结合的转化潜力。