The mystery of atherosclerosis.

Groundbreaking Research Rewrites Understanding of Atherosclerosis

A significant breakthrough in medical research is quietly revolutionizing our understanding of atherosclerosis, potentially rendering stent surgeries obsolete. A recent study published in the prestigious journal Nature, led by Professor Kong Wei from Peking University's School of Basic Medical Sciences, in collaboration with Professor Sun Jinping from Peking University/Shandong University, Professor Jiang Changtao from Peking University, and Professor Zheng Jinguang from Peking University People's Hospital, has made a startling discovery. The study, titled "Sensing ceramides by CYSLTR2 and P2RY6 to aggravate atherosclerosis," has successfully unraveled the mysteries of atherosclerosis formation, capturing the crucial moment that determines the fate of millions – the three-dimensional structure of the ceramide receptor complex.

While analyzing blood samples from 4,236 coronary heart disease patients, Professor Kong Wei's team made a startling discovery: every 1 μmol/L increase in ceramide concentration per microliter of blood corresponds to a 3.7% expansion of coronary artery plaque volume. If the detected value reaches the warning threshold, the patient's plaque volume may double within five years. Ceramides not only promote the growth of plaques but also activate the "self-destruction program" of macrophages, inducing them to engulf oxidized low-density lipoprotein (LDL) and eventually form deadly foam cells. Ceramides are the core driving force behind plaque growth.

The research team identified the endogenous membrane receptor for long-chain ceramides as cysteinyl leukotriene receptor 2 (CYSLTR2) and purinergic receptor P2Y6. When these receptors recognize ceramides, they trigger the activation of Gq protein, leading to the activation of inflammatory bodies and significantly exacerbating the formation of atherosclerotic plaques. The study also explored the role of long-chain ceramides in worsening atherosclerosis in patients with chronic kidney disease (CKD). By analyzing blood plasma samples from CKD patients with different stages of kidney function, the team confirmed an independent correlation between ceramide levels and the severity of coronary artery disease.

The study's findings have far-reaching implications for the prevention and treatment of atherosclerosis. Targeting CYSLTR2/P2RY6 with small-molecule inhibitors or antibody drugs may become a novel strategy for combating atherosclerosis. By detecting blood ceramide spectra and receptor gene polymorphisms, clinicians may be able to accurately stratify cardiovascular risk and tailor personalized treatment plans for patients. Several world-renowned medical institutions, including the Mayo Clinic, have already begun measuring patient blood ceramide levels to assess cardiovascular disease risk. Multiple pharmaceutical companies have also initiated drug development programs targeting ceramide-related pathways.

However, it is essential to note that ceramides are crucial components of cell membranes, and targeting their metabolism may lead to side effects. Nevertheless, this groundbreaking research brings new hope and possibilities for humanity's fight against atherosclerosis. As we look to the future, we can expect revolutionary changes in the prevention and treatment of cardiovascular disease.