Monocyte DPP4 Expression in Human Atherosclerosis Is Associated With Obesity and Dyslipidemia

Studies including ours indicate that systemic inhibition of dipeptidyl peptidase 4 (DPP4), an ubiquitously expressed peptidase, by pharmaceutical inhibitors improved atherosclerosis (1,2). However, the role of immune cell–derived DPP4 is not well defined in atherosclerosis. Our previous work demonstrated that DPP4 expression on monocytes/macrophages was increased in obesity and associated with the degree of insulin resistance (3). To test if the obesity-related increase of monocyte DPP4 plays a role in vascular disease, we investigated the relationship of monocyte DPP4 expression with human aortic atherosclerosis, obesity, and lipid metabolism. A total of 14 control volunteers and 27 atherosclerotic patients without diagnosed heart, lung, or liver diseases and without prescription drugs (except ACE inhibitors and angiotensin receptor blockers) were selected from Aliskiren Effect on Aortic Plaque Progression (ALPINE), a phase 4 clinical trial (clinical trial reg. no. NCT01417104, clinicaltrials.gov). Presence of aortic atherosclerotic plaque (Fig. 1 A ) was confirmed by high-resolution three-dimensional MRI. Figure 1 A : High-resolution three-dimensional dark-blood MRI was used to confirm the aortic atherosclerotic plaque in patients with atherosclerotic disease. Arrows indicate the thickening of the aortic wall. Scale bars, 10 mm. B and C : DPP4 expression on circulating immune cells. Peripheral blood mononuclear cells were isolated from healthy volunteers, and CD11b+ monocyte and CD3+ T cells were gated for …