Development of Individualized Therapy for Atherosclerosis from Systems Biology

Myocardial infarction (MI) and ischemic stroke (IS), major consequences of unstable atherosclerotic lesions, are the most common causes of death worldwide. Guidance for prevention of MI and IS is currently based on treatment efficacy at the group level, but it is increasingly reported that distinct individual-level disease phenotypes exist in atherosclerotic cardiovascular disease (CVD), suggesting differing optimal therapies and room for improved personalized care. Whereas personalized cancer treatment strategies have been developed based on information from tissue biopsies, such approaches have previously not been possible for CVD. However, utilizing noninvasive imaging for detailed morphological phenotyping to obtain quantitative imaging biomarkers of atherosclerotic lesions, combined with large-scale molecular profiling of plaque tissue retrieved at stroke-preventive carotid surgery (endarterectomy), we have been able to create individually calibrated systems biology models capable of generating individualized guidance strategies for surgical treatment and pharmacotherapy. In this chapter, we summarize the work behind these translational research advances, which currently stand next to implementation in clinical practice for improved precision in prevention of MI and IS.