O papel do gene TREML4 no desenvolvimento de lesões ateroscleróticas

Abstract

Cardiovascular diseases (CVD) represent the highest percentage of morbidity and mortality in the world and its main cause is atherosclerosis. Atherosclerosis. is a multifactorial and inflammatory disease that has a long asymptomatic phase and commonly starts during childhood. Therefore, the accurate identification of atherosclerosis. is the starting point for the implementation of effective strategies for the primary prevention of CVD. TREML4 is a member of the immunoglobulin superfamily expressed in different cell types of the immune system, such as monocytes and macrophages and is related to CVD. We analyzed by qRT-PCR and genotyping the gene expression and polymorphisms (rs2803495 and rs2803496) of TREML4 in patients with Coronary Artery Disease (CAD) (n=137), Subclinical Atherosclerosis (340) and PostAcute Infarcted Left Ventricular Dysfunction of the Myocardium (AMI) (65). Subjects carrying the minor alleles (G and C) have higher expression of TREML4 (OR 8.01, 95% CI 3.78 - 16.99, p <0.001 and OR 10.42, 95% CI 4.76 - 22 .78, p<0.001, respectively). Patients with major coronary artery lesions have greater expression of TREML4 than individuals without or with low and intermediate lesions (p<0.005). No association was observed between TREML4 expression and AS or LV dysfunction post-AMI (p>0.05). Through the in silico approach, we identified the miRNAS: miR-181a-5p, miR-200b-3p, miR-24-3p, miR-296-5p, miR-361-5p, miR-423-5p, miR-486- 3p and miR-708-5p potentially associated with TREML4. Thus, our results confirm that genetic polymorphisms influence TREML4 expression and that TREML4 expression is a potential biomarker for key steps in the progression of atherosclerosis and is not related to events prior to CAD and Acute Coronary Syndrome. Furthermore, we propose that 8 miRNAs differentially expressed in patients with CAD may be associated with inflammatory pathways potentially regulated by TREML4.