Atherosclerosis remains a leading cause of cardiovascular morbidity and mortality worldwide, yet therapeutic outcomes vary significantly among patients. Current pharmacological interventions target broad pathways implicated in vascular smooth muscle cell (vSMC) dysfunction and plaque stability; however, patient-specific responses to these therapies remain poorly understood. This research seeks to investigate drug response profiles in patient-derived vSMCs to enable tailored therapeutic strategies for atherosclerosis management. Patient-derived vSMCs will be isolated from calcified atherosclerotic plaques and adjacent healthy arterial tissue collected during carotid endarterectomy. By comparing the therapeutic responses of vSMCs from diseased and healthy tissues, this study aims to uncover differential drug efficacy and identify molecular determinants of responsiveness. A key hypothesis is that vSMCs from calcified plaques exhibit distinct pharmacological profiles compared to those from healthy arterial regions due to underlying phenotypic shifts and molecular alterations.
The primary objectives of this research are to: (1) characterize the phenotypic and molecular differences between vSMCs from calcified plaques and adjacent healthy tissue, (2) evaluate the responses of these cells to existing pharmacological treatments (statins, ezetimibe, PCSK9 inhibitor) for atherosclerosis, and (3) identify biomarkers predictive of drug efficacy in vSMCs. The findings are expected to advance our understanding of the heterogeneity in drug responses in atherosclerosis and lay the groundwork for precision medicine approaches in its treatment.
This patient-oriented approach integrates patient cellular and tissue analyses to bridge the gap between bench research and clinical outcomes. By leveraging patient-derived samples, this study directly addresses the need for individualized therapeutic strategies, ultimately aiming to improve the efficacy and safety of atherosclerosis treatments tailored to each patient’s unique vascular biology.