Abstract 15377: The Role Homeostatic Chemokines CCl19 and CCl21 in Carotid Atherosclerosis
Objective: We have previously shown that the chemokines CCL19 and CCL21 and their common receptor CCR7 are involved in coronary artery disease. Within atherosclerotic lesions, these chemokines were localized to vascular smooth muscle cells (SMC). Here we extend these previous studies by examining the expression of these chemokines in patients with carotid atherosclerosis and their effects on smooth muscle cells.
METHODS AND Results: We used ELISA to measure the plasma levels of CCL19 and CCL21 in patients with symptomatic (n=99), asymptomatic (n=59) carotid disease and healthy controls (n=26). We found an increased level of CCL21, but not CCL19, in patients with carotid atherosclerosis with particularly high levels in those with symptomatic disease. Gene transcripts of CCL19, CCL21 and their receptor CCR7 were analyzed by qPCR in plaques from patients with asymptomatic (n=7) and symptomatic (n=14) carotid plaques. Within the carotid plaques, patients with symptomatic disease have significantly increased expression of both CCL19 and CCL21, but not CCR7, as compared with patients with asymptomatic lesions. To study effects of CCL19 and CCL21 were examined on aortic SMC. In vitro, CCL19, but not CCL21, promoted a proliferative and secretory SMC phenotype, as assessed by increased radiolabelled thymidine incorporation and matrix metalloproteinase secretion, respectively.
Conclusions: The homeostatic chemokines CCL19 and CCL21 showed enhanced expression in patients with carotid atherosclerosis, both systemically (CCL21) and within the plaques (CCL19 and CCL21). In vitro, CCL19 but not CCL21 promoted a proliferating and matrix degrading phenotype suggesting a different role for the two chemokines in plaque progression.
- © 2012 by American Heart Association, Inc.