Proinflammatory CD14+CD16+ Monocytes Are Associated With Subclinical Atherosclerosis in Renal Transplant Patients

Abstract

Atherosclerotic cardiovascular disease is a major cause of death in renal transplant (TX) recipients. Atherosclerotic lesions are characterized by monocytic infiltration. Circulating monocytes can be divided into functionally distinct subpopulations, among which CD14++CD16+ and CD14+CD16+ monocytes (summarized as CD16+ monocytes) are proinflammatory cells. We hypothesized that the frequency of circulating CD16+ monocytes is associated with subclinical atherosclerosis in TX patients. Monocyte subpopulations were quantified in 95 TX and 31 hemodialysis patients (HD). In TX patients, subclinical atherosclerosis was determined by carotid intima media thickness (IMT) measurement. TX patients had lower frequencies of CD16+ monocytes than HD patients. When stratifying by immunosuppressive treatment, patients on methylprednisolone (MP) therapy had fewer CD14+CD16+ monocytes than patients not receiving MP. CD14+CD16+ monocytes decrease very shortly after transplantation. CD14+CD16+ monocyte frequency correlated with IMT in TX recipients (r = 0.34, p < 0.001). This correlation was most pronounced among patients without MP treatment (r = 0.55, p = 0.02). In a multivariate regression analysis, the association of CD14+CD16+ monocytes with IMT was independent from traditional cardiovascular risk factors. The frequency of proinflammatory CD14+CD16+ monocytes is independently associated with subclinical atherosclerosis in transplant recipients. Further studies on the association between circulating leukocytes and atherosclerosis should take monocyte heterogeneity into account.

Vitamin D Suppression of Endoplasmic Reticulum Stress Promotes an Antiatherogenic Monocyte/Macrophage Phenotype in Type 2 Diabetic Patients

“…Multiple studies in nondiabetics suggest a positive correlation between the proportion of circulating CD14 lo /CD16 ϩ monocytes and proinflammatory markers or carotid intimamedia thickness (3,4,48), but no significant differences are found in the mean percentages of CD14 lo /CD16 ϩ monocytes between patients with uncomplicated diabetes, diabetics with cardiovascular disease, and control subjects (5). In this study of diabetic patients, classification of monocyte subtypes based on CD14 and CD16 expression did not correlate with 25(OH)D level or with functional adhesion, suggesting that different monocyte markers could better characterize the functions con-FIGURE 6.…”

Effect of Different Dialysis Modalities on Microinflammatory Status and Endothelial Damage

“…CD14 ϩ CD16 ϩ cells have been described as a subset of human peripheral monocytes that are phenotypically more differentiated than CD14 ϩϩ and produce proinflammatory cytokines, such as TNF and IL-6 (10,11). In addition, a higher percentage of CD14 ϩ CD16 ϩ monocytes is correlated with endothelial damage in CKD patients (12) and, interestingly, the high levels of CD14 ϩ CD16 ϩ also predicted the appearance of cardiovascular disease. Recently, we reported that a decrease in the percentage of proinflammatory CD14…”

Monocyte Angiotensin Converting Enzyme Expression May Be Associated with Atherosclerosis Rather than Arteriosclerosis in Hemodialysis Patients

“…By infiltrating the vessel wall, Mo2 cells carry ACE into the plaque (13), making the enzyme that produces the highly proinflammatory and pro-oxidative angiotensin II (14) available within the vessel wall lesion. In several independent cohorts, we recently reported an association between elevated counts of Mo2 monocytes and subclinical (15) or manifest atherosclerosis (16,17) as well as cardiovascular outcome (11,16 -19). Furthermore, the level of ACE expression in the Mo2 monocyte population proved to be highly predictive of mortality in dialysis patients (19).…”