Abstract 582: The CCR7+ PDGFRa+ Cell Population is Increased in Regressing Atherosclerotic Plaques

Abstract

Introduction: Atherosclerosis is characterized by the accumulation of lipids, cells and fibers in the arterial wall. Atherosclerotic plaques form in regions of low blood flow, whereas vessels exposed to high blood flow remain lesion-free. We created a surgical mouse model, arteriovenous fistula (AVF), which increases blood flow in the brachiocephalic artery (BCA) specifically, without altering serum lipid levels. Methods & Results: LDLR KO mice were placed on a high-fat diet (HFD). Control mice were sacrificed at week 12. Sham and AVF surgery was performed at week 12 and mice were kept on a HFD for a further 1-4 weeks. We found that high blood flow is beneficial and leads to a significant ~50% regression of BCA plaque size in AVF mice compared with Controls, by week 4. We performed flow cytometry to characterize the different cell populations within Sham and AVF plaques. At day 7 after surgery, there was no difference in macrophage (F4/80+) or dendritic cell (CD11c+) content between Sham and AVF. However, we found a significant, 4-fold increase in the total number of CD45-/CCR7+/PDGFRa+ cells in the BCA plaques of AVF mice vs Shams (p<0.01). No such change was observed in the aortic sinus plaques of AVF or Shams. CCR7 was previously found to be overexpressed in regressing plaques upon an abrupt lowering of plasma lipids, but in CD45+ cells. In our model, plasma lipids remained high and CCR7+ cells instead expressed PDGFRa, a perivascular and multi-lineage differentiation marker. This cell population also expressed mesenchymal stem cell markers (CD90, CD44, CD34) and CD68. Conclusion: Our data point to an unexpected increase in the CD45-/CCR7+/PDGFRa+ cell population in the early plaque regression process. They suggest that mesenchymal-type cells may promote regression in plaques exposed to high blood flow.