Increased expression of monocytic angiotensin-converting enzyme in dialysis patients with cardiovascular disease.

BACKGROUND: Patients with chronic renal disease suffer from accelerated atherogenesis, which is promoted by inflammation and oxidative stress. Tissue angiotensin converting enzyme (ACE) exerts proinflammatory and prooxidative effects by producing angiotensin II. Monocytes are strongly involved in the pathogenesis of atherosclerosis. They express ACE, which might contribute to their atherogenic potency. We hypothesize that dialysis patients have increased monocytic ACE expression, and that ACE expression on circulating monocytes is associated with prevalent cardiovascular disease.
METHODS: In 74 dialysis patients, ACE expression on total monocytes and monocyte subsets was measured flow-cytometrically in a whole-blood assay. A subpopulation of 22 dialysis patients was compared to an age- and gender-matched control group with intact renal function. Cardiovascular risk factors and the prevalence of cardiovascular disease were assessed. In a subgroup of patients (n = 8), monocytic ACE activity was measured in vitro and correlated with monocytic ACE expression.
RESULTS: Dialysis patients had an increased expression of monocytic ACE compared to controls. Monocytic ACE expression was higher in dialysis patients with prevalent cardiovascular disease than in those without cardiovascular disease. This association remained significant after correction for classical cardiovascular risk factors. Among monocyte subsets, CD14++CD16+ monocytes had the highest ACE expression. Monocytic ACE activity correlated with ACE surface expression.
CONCLUSIONS: The finding of increased ACE expression on monocytes of dialysis patients with cardiovascular disease links monocytes to the activated renin-angiotensin system. ACE expression was found highest among CD14++16+ monocytes, which is in accordance with a prominent role of these proinflammatory cells in atherogenesis.