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

Abstract

SummaryBackground and objectives Circulating monocytes can be divided into functionally distinct subpopulations according to their surface expression of CD14 and CD16. Monocytes with high-level expression of both antigens (CD14 ϩϩ CD16 ϩ , Mo2 cells) are associated with cardiovascular morbidity and mortality in hemodialysis patients. These cells express angiotensin converting enzyme (ACE) on their surface. They are involved in the association of chronic inflammation and cardiovascular disease in kidney patients. Cardiovascular morbidity results from atherosclerosis (plaque-forming, vessel occluding disease) and arteriosclerosis (loss of arterial dampening function). It is unknown whether ACE-expressing proinflammatory monocytes are related to atherosclerosis, arteriosclerosis, or both.Design, setting, participants, & measurements During baseline examination for a prospective study on monocyte ACE expression and mortality, 60 chronic hemodialysis patients of an academic outpatient center were screened for atherosclerosis by carotid artery ultrasound, for arteriosclerosis by pulse pressure measurement, and for ACE expression on Mo2 cells by flow cytometry.Results ACE expression on Mo2 monocytes was significantly higher in patients with severe compared with those with little or no carotid atherosclerosis. Mo2 ACE correlated with a score to semiquantify atherosclerosis and remained a significant predictor of carotid plaques in multivariate analysis including the other univariately associated variables of age, hemoglobin A1c, and albumin. Mo2 ACE was not related to pulse pressure.Conclusions ACE expression on Mo2, although being a known predictor of mortality and cardiovascular disease in end-stage renal disease patients, may act via enhancement of atherosclerosis rather than arteriosclerosis.

Human monocyte subsets exhibit divergent angiotensin I-converting activity

“…Ang II exerts its pressor action via type 1 receptor (AT1). However, other types of receptors to Ang II (such as type 2 receptor responsible for vasodilatation -AT2) and also angiotensins produced by alternative cleavage pathways, namely by ACE2, and including angiotensins 1-9 and 1-7 [Ang- (1)(2)(3)(4)(5)(6)(7)(8)(9) and Ang-(1-7), respectively], have been discovered. Importantly, they may activate other signalling pathways ( Fig.…”

Post-Dilution High Convective Transport Improves Microinflammation and Endothelial Dysfunction Independently of the Technique

“…CVD is closely related to chronic inflammation in hemodialysis (HD) patients [2]. Inflammation has been associated with activation of mononuclear cells in these patients [3]. CD14 + CD16 + cells have been described as a subset of human peripheral monocytes that produce proinflammatory cytokines, such as TNF and IL-6 [4].…”

Differential Expression of Lipoprotein-Associated Phospholipase A2 in Monocyte Subsets: Impact of Uremia and Atherosclerosis

“…It is of note that non-classical monocytes of A+ patients show an increased Lp-PLA2 mRNA expression profile in comparison to A-patients, but indeed we have to keep in mind that Lp-PLA2 expression is mainly expressed by the classical subsets. The meaning of it, however, remains obscure at the moment, and the role of Lp-PLA2 expression in the recently described proatherogenic intermediate monocyte subset [2,3] has to be addressed in further studies.…”

“…We recently succeeded in demonstrating that inflammatory monocytes (CD14++CD16+ and CD14++ CD16+) expressing high ACE levels are linked to atherosclerosis and may be part of the inflammatory circle in atherosclerotic plaques [2,3] .…”