Inflammation reprogramming and immunomodulation: Next-generation treatments for atherosclerosis
Robin P. Choudhury, Rupen Hargreaves, Jason Chai, Edward A. Fisher
Abstract
The current generation of highly successful atherosclerosis treatments, such as low-density lipoprotein (LDL)-cholesterol reduction, blood pressure management, and smoking cessation, has largely focused on ameliorating factors perceived to drive incident disease and its complications. The adverse contributions of these factors have typically been identified through epidemiological studies. The therapeutic strategies that arose in response focused on risk factors for disease development and tended to overlook the fact that patients already have established disease, by the time of presentation. However, by capitalizing on contemporary biological knowledge and technologies, it is becoming increasingly possible to shift from a model based on population-derived risk factor management to next-generation treatments (including monoclonal antibodies, small interfering RNA [siRNA], mRNA, epigenetic reprogramming, and gene editing) for atherosclerosis that are tailored to patient-level disease processes, informed by mechanistic characterization, offer potential to reverse or regress disease, and incorporate systems-level interventions that extend beyond the atherosclerotic plaque. Choudhury et al. explore next-generation atherosclerosis therapies. They identify a shifting focus from risk factor management alone to patient-specific, mechanistically informed treatments. Leveraging advanced technologies (cell therapies, monoclonal antibodies, siRNA, mRNA, and gene editing), emerging approaches intend to reverse or regress established disease and incorporate systems-level interventions beyond the atherosclerotic plaque.