Margulies Kenneth B, Bednarik Daniel P, Dries Daniel L
Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Am Coll Cardiol. 2009 May 12;53(19):1752-9. doi: 10.1016/j.jacc.2008.12.064.
Associated with technological progress in deoxyribonucleic acid and messenger ribonucleic acid profiling, advances in basic biology have led to a more complete and sophisticated understanding of interactions among genes, environment, and affected tissues in the setting of complex and heterogeneous conditions such as heart failure (HF). Ongoing identification of mutations causing hereditary hypertrophic and dilated cardiomyopathies has provided both pathophysiological insights and clinically applicable diagnostics for these relatively rare conditions. Genotyping clinical trial participants and genome-wide association studies have accelerated the identification of much more common disease- and treatment-modifying genes that explain patient-to-patient differences that have long been recognized by practicing clinicians. At the same time, increasingly detailed characterization of gene expression within diseased tissues and circulating cells from animal models and patients are providing new insights into the pathophysiology of HF that permit identification of novel diagnostic and therapeutic targets. In this rapidly evolving field, there is already ample support for the concept that genetic and expression profiling can enhance diagnostic sensitivity and specificity while providing a rational basis for prioritizing alternative therapeutic options for patients with cardiomyopathies and HF. Although the extensive characterizations provided by genomic and transcriptional profiling will increasingly challenge clinicians' abilities to utilize complex and diverse information, advances in clinical information technology and user interfaces will permit greater individualization of prevention and treatment strategies to address the HF epidemic.
随着脱氧核糖核酸和信使核糖核酸分析技术的进步，基础生物学的进展使人们在诸如心力衰竭（HF）这种复杂和异质性的情况下，对基因、环境和受影响组织之间的相互作用有了更完整、更深入的理解。对导致遗传性肥厚型和扩张型心肌病的突变的持续识别，为这些相对罕见的疾病提供了病理生理学见解和临床适用的诊断方法。对临床试验参与者进行基因分型以及全基因组关联研究，加速了对更为常见的疾病修饰基因和治疗修饰基因的识别，这些基因解释了临床医生长期以来所认识到的患者个体差异。与此同时，对动物模型和患者患病组织及循环细胞内基因表达的日益详细的表征，为心力衰竭的病理生理学提供了新的见解，从而有助于识别新的诊断和治疗靶点。在这个快速发展的领域，基因和表达谱分析能够提高诊断的敏感性和特异性，同时为心肌病和心力衰竭患者选择替代治疗方案提供合理依据，这一概念已经得到了充分支持。尽管基因组和转录谱分析所提供的广泛特征将越来越挑战临床医生利用复杂多样信息的能力，但临床信息技术和用户界面的进步将使预防和治疗策略更具个性化，以应对心力衰竭的流行。
