CD14+CD16++ “nonclassical” monocytes are associated with endothelial dysfunction in patients with coronary artery disease

Abstract

Endothelial dysfunction and inflammation are key mechanisms of vascular disease. We hypothesised that heterogeneity of monocyte subpopulations may be related to the development of vascular dysfunction in coronary artery disease (CAD). Therefore, we examined the relationships between monocyte subsets (CD14CD16 "classical - Mon1", CD14CD16 "intermediate - Mon2" and CD14CD16 "nonclassical - Mon3"), endothelial function and risk factor profiles in 130 patients with CAD undergoing coronary artery bypass grafting. This allowed for direct nitric oxide (NO) bioavailability assessment using isometric tension studies ex vivo (acetylcholine; ACh- and sodium-nitropruside; SNP-dependent) in segments of internal mammary arteries. The expression of CD14 and CD16 antigens and activation markers were determined in peripheral blood mononuclear cells using flow cytometry. Patients with high CD14CD16 "nonclassical" and low CD14CD16 "classical" monocytes presented impaired endothelial function. High frequency of CD14CD16 "nonclassical" monocytes was associated with increased vascular superoxide production. Furthermore, endothelial dysfunction was associated with higher expression of activation marker CD11c selectively on CD14CD16 monocytes. Nonclassical and classical monocyte frequencies remained independent predictors of endothelial dysfunction when major risk factors for atherosclerosis were taken into account (β=0.18 p=0.04 and β=-0.19 p=0.03, respectively). In summary, our data indicate that CD14CD16 "nonclassical" monocytes are associated with more advanced vascular dysfunction measured as NO- bioavailability and vascular reactive oxygen species production.

Oxidative Stress, Inflammation, and Vascular Aging in Hypertension

“…17,[67][68][69][70] Oxidative stress is central in the pathology both as an initiator of vascular and renal inflammation and the consequence of inflammatory responses and cytokines. [71][72][73] This is particularly important, in light of the role of immunosenescent T cells in hypertension and the susceptibility of T cells to changes associated with aging.…”

“…79 Although antibodies seem to be important, B cells may exert their effects through B-cell specific contribution to cytokine production, such as tumor necrosis factor-α, 80 which has been shown to be prohypertensive and proatherosclerotic. Role of macrophages in hypertension and atherosclerosis is evident 67,81 and closely linked to NADPH oxidases, which are abundant within both monocytes and macrophages. 82 Nox2 NADPH oxidase mediates M1/M2 polarization and regulates their participation in vascular damage, inflammation, and fibrosis.…”

The origins and homeostasis of monocytes and tissue‐resident macrophages in physiological situation

“…In humans, monocyte subsets in blood were roughly defined as classical CD14 ++ CD16 − CCR2 + monocytes, intermediate CD14 ++ CD16 + CCR2 + monocytes and nonclassical CD14 + CD16 ++ CCR2 − monocytes according to the contemporary nomenclature (Ziegler‐Heitbrock et al, ), which have been summarized in Table . The intermediate CD14 ++ CD16 + monocyte subset in humans represents the smallest monocyte population in blood and can produce large amount of TNF‐α after LPS stimulation (Schlitt et al, ; Urbanski et al, ). In mice, monocytes in peripheral blood can be divided into the classical Ly6C high/+ CD43 + monocytes, the intermediate Ly6C high/+ CD43 high/+ monocytes, and the patrolling nonclassical Ly6C low/− CD43 high/+ monocytes.…”

“…In humans, monocyte subsets in blood were roughly defined as (Schlitt et al, 2004;Urbanski et al, 2017). In mice, monocytes in peripheral blood can be divided into the classical Ly6C high/+ CD43 + monocytes, the intermediate Ly6C high/ + CD43 high/+ monocytes, and the patrolling nonclassical Ly6C low/ − CD43 high/+ monocytes.…”

Involvement of CD8+ T cell subsets in early response to vascular injury in patients with peripheral artery disease in vivo

“…Immune responses to modified lipoproteins (such as minimally oxidized / B phenotype / small dense LDLs) have been identified as key initiators of atherosclerotic plaque development [3]. This is linked to immune cell recruitment into the vessel wall, which is facilitated by endothelial dysfunction and increased expression of adhesion molecules and immune cell recruitment [4, 5]. T cells are one of the cells recruited early to the dysfunctional vasculature and may precede and orchestrate recruitment of key cells including pro-atherosclerotic macrophages, neutrophils or B cells.…”