The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis.

Metabolic syndrome (MetS) is a cluster of interrelated and co-occurring metabolic disorders, including abdominal obesity, hyperglycemia, dyslipidemia, the reduced high-density lipoprotein (HDL) cholesterol, and/or hypertension. Cardiovascular diseases are the leading causes of death and disability in metabolic syndrome. Each component of MetS is an independent risk factor for cardiovascular diseases, and the combination of these factors can increase the incidence and severity of cardiovascular diseases, such as atherosclerosis, myocardial infarction, and heart failure, with atherosclerosis being the primary cause of cardiovascular-related death in MetS. The specific pathogenic mechanism in the occurrence and development of atherosclerosis in MetS is still not fully understood. An increasing number of studies have shown that the purinergic signaling pathway plays a significant role in atherosclerosis. ATP and ADP, key signaling molecules in the purinergic signaling pathway, are not only involved in cellular energy metabolism but also activate the purinergic signaling pathway by binding to P1 and P2 purinergic receptors (P1R and P2R), regulating vascular contraction and relaxation, and inhibiting platelet aggregation. Purinergic signaling can act as both a promoter and a resistance factor in the formation of atherosclerosis, depending on the receptor subtype and downstream signaling network. This review summarizes the specific roles and mechanisms of the purinergic signaling network in MetS-related atherosclerosis and analyzes the clinical application of targeting the purinergic signaling pathway, providing a theoretical basis and innovative ideas for basic research and clinical treatment in this field.