The Relationship Between Peripheral Blood M6A Methylation Level And Plaque Vulnerability In Patients With Acute Coronary Syndrome

Background: Atherosclerosis(AS)is regarded as one of the leading causes of cardiovascular disease(CVD).At the same time,the unpredictable rupture of fragile plaques can result in adverse cardiovascular outcomes,such as acute coronary syndrome(ACS),or even sudden cardiac death.Some high-risk plaque features are closely related to plaque vulnerability and ultimately affect the prognosis of patients.Therefore,it is of great significance to evaluate the vulnerability of atherosclerotic plaques and to intervene early to reduce the mortality of coronary artery disease.Optical coherence tomography(OCT),an intravascular imaging technique,can take advantage of its high resolution to visually identify the microscopic morphological features of coronary plaques,which is critical for the identification of potentially vulnerable plaques.However,the extensive application of OCT is limited due to the invasive examination and its relatively high cost.Therefore,it is particularly important to find a non-invasive,convenient and low-cost detection method.In recent years,epitranscriptomics has become an emerging research field in explaining the pathogenesis of atherosclerosis.N6-methyladenosine(m6A)is one of the most common types of RNA chemical modification.Currently,an increasing number of studies have focused on the relationship between m6 A modification and human systemic disease,such as diseases of the nervous system,tumours,viral infections,metabolic diseases and cardiovascular disease etc.Many studies have shown that m6 A modification is closely related to the metabolism of atherosclerotic tissues and cells.However,the relationship between m6 A modification and coronary plaque instability remains to be elucidated.Objective: The purpose of this study was to explore the association between the overall m6A level of peripheral blood mononuclear cell(PBMCs)RNA in patients with ACS and the plaque vulnerability of coronary culprit lesions by OCT,so as to detect the potential role of m6A modification in coronary plaque instability and provide more possibilities for the treatment or prevention of plaque rupture.Methods:112 subjects diagnosed with ACS who underwent coronary angiography(CAG)and OCT examination were screened during the period from Jan 2021 to Jun2021.After excluding 7 cases with poor OCT images and5 cases with missing and unavailable blood samples,the data of 66 patients were analyzed statistically according to the corresponding exclusion criteria.All subjects were divided into two groups(T1and T2)based on the median absolute quantification of total m6A modification of peripheral blood RNA as measured by colorimetry.Baseline clinical data,medical history,laboratory indicators,and OCT imaging features of the coronary culprit lesions were collected from these patients,and qualitative and quantitative indicators of plaques at the culprit lesions were measured.Results:1.Except for m6A levels in peripheral blood,demographic characteristics and laboratory results were comparable between the two groups.2.Coronary angiography showed that there were no differences in the distribution of coronary culprit vessels and the location of the lesion(p>0.05).The location of the lesion was concentrated in the proximal part of the vessel.In addition,there were no statistically significant in lesion length and diameter stenosis percentage between groups(p>0.05).3.OCT imaging analysis suggested that the the T1 group with low m6A level had thinner fiber cap thickness,bigger maximum lipid arc,larger lipid core length,and smaller area stenosis percentage.Patients in T1 group had bigger maximum lipid arc(p=0.049).Similarly,the incidence of lipid-rich plaque(75.8%vs.48.5%,p=0.022)and TCFA(48.5%vs.24.2%,p=0.041)was significantly greater in the T1 group,while the incidence of fibrous calcification(6.1%vs.30.3%,p=0.011)was lower in the T1 group.4.Multivariate logistic regression analysis showed that after adjusting for age,hypertension,diabetes,and current smokers and taking T1 group as a reference,the risk of lipid-rich plaque(OR(95%CI),0.275(0.092-0.825);p=0.021)and TCFA(OR(95%CI),0.324(0.107-0.983);p=0.047)were significantly reduced in the T2 group,but the risk of fiber calcification in the T2 group(OR(95%CI),8.425(1.515-46.838);p=0.015)increased significantly.Conclusion:1.The low methylation of m6A RNA in peripheral blood is independently correlated with the vulnerability of coronary plaques,suggesting that m6A modification may be involved in the occurrence and development of unstable plaques.2.The level of m6A RNA methylation in peripheral blood may serve as a non-invasive potential biomarker for clinical prediction of plaque features that may represent unstable plaques.This is effective in preventing acute cardiovascular events secondary to vulnerable plaques in advance.