Results in Chemistry (Dec 2024)
PD-1 agonist: A novel therapeutic approach to resolve atherosclerosis
Abstract
Atherosclerosis, which is the primary cause of several leading fatal diseases worldwide, has long been a challenge, and thus the need for effective treatments is urgent. The discovery of the immune checkpoint proteins programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1), which are negative regulators that inhibit immune responses, has led to the development of immunotherapeutic strategies for the management of atherosclerosis. Atherosclerosis mainly occurs as an adaptive immune response that results in an increased ratio of M1/M2 macrophages, and PD-1 can suppress this increased ratio through T-cell-mediated and macrophage-mediated pathways, thus controlling the course of atherosclerotic inflammation. Currently, 6 confirmed PD-1 agonists have been shown to inhibit inflammatory processes, which indicates the potential of PD-1 agonists as drugs for the treatment of atherosclerosis and other inflammatory diseases. PD-1 agonists have demonstrated their anti-inflammatory effects in both preclinical studies and clinical trials. These drugs also show considerable clinical potential when used in combination with aspirin and statins. In the future, PD-1 agonists are expected to become a novel treatment for atherosclerosis and other inflammatory diseases.