261 - oxLDL receptor in lymphocytes prevents atherosclerosis and predicts subclinical disease (ID 46)
Abstract
Background and Aims
The role of Th17 and Treg cells in the progression of atherosclerosis remain elusive. We aimed to evaluate the association between the CD69 receptor, a regulator of Th17/Treg immunity, and atherosclerosis development in animal models and in patients with subclinical disease.
Methods
Ldlr-/- chimeric mice expressing or not CD69 were subjected to high fat diet and atherosclerosis was analyzed. Expression of CD69 and NR4A nuclear receptors was evaluated by RT-PCR in male participants of the Progression of Early Subclinical Atherosclerosis (PESA) study, with extensive (n=128) or focal (n=55) atherosclerosis and without disease (n=122).
Results
Mice lacking CD69 on lymphoid cells developed large atheroma plaque along with an increased Th17/Treg ratio in blood. OxLDL was shown to bind specific to CD69 on human T lymphocytes, inhibiting the development of Th17 cells through the activation of NR4A nuclear receptors. Participants of the PESA study with evidence of subclinical atherosclerosis displayed a significant CD69 and NR4A1 mRNA downregulation in peripheral blood leukocytes compared with participants without disease. The expression of CD69 remained associated with the risk of subclinical atherosclerosis in an adjusted multivariable logistic regression model (odds ratio, 0.62; 95% confidence interval, 0.40-0.94; P=0.006) after adjustment for traditional risk factors, the level of oxLDL, and the counts of different leucocytes subsets.
Conclusions
CD69 depletion from the lymphoid compartment exacerbates the development of atherosclerosis. CD69 binding to oxLDL on T cells induces the expression of anti-inflammatory transcription factors. The expression of CD69 remained as an independent predictor of subclinical atherosclerosis after adjustment for traditional risk factors.
