TY - JOUR
T1 - Impact of Mon2 monocyte-platelet aggregates on human coronary artery disease
AU - Brown, Richard A
AU - Lip, Gregory Y H
AU - Varma, Chetan
AU - Shantsila, Eduard
N1 - © 2018 Stichting European Society for Clinical Investigation Journal Foundation.
PY - 2018/5
Y1 - 2018/5
N2 - INTRODUCTION: Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown.METHODS: Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium dependent vasodilation) and sodium nitroprusside (endothelium independent vasodilation) at 100μA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months.RESULTS: Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (p=0.001) and patients without CAD (p=0.006). On multivariate regression MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, p=0.01) and correlated negatively with endothelium-dependent microvascular vasodilation (r= -0.37, p=0.008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed persistence of an inverse relationship between MPAs with Mon2 and endothelial-dependent microvascular function.CONCLUSION: MPAs with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction. This article is protected by copyright. All rights reserved.
AB - INTRODUCTION: Monocyte-platelet aggregates (MPAs) form when Mon1, Mon2 or Mon3 monocyte subsets adhere to platelets. They are pathophysiologically linked to coronary artery disease (CAD). However, their individual roles in the occurrence of diffuse CAD remain unknown.METHODS: Peripheral blood from 50 patients with diffuse CAD, 40 patients with focal CAD and 50 age-matched patients with normal coronary arteries was analysed by flow cytometry to quantify MPAs associated with individual monocyte subsets. Cutaneous forearm microcirculation was assessed using laser Doppler flowmetry at rest and after iontophoresis of acetylcholine (endothelium dependent vasodilation) and sodium nitroprusside (endothelium independent vasodilation) at 100μA for 60 seconds. Patients with CAD had repeat assessment at 6 and 12 months.RESULTS: Baseline counts of MPAs with Mon2 subset (CD14++CD16+CC2+ monocytes) were significantly higher in patients with diffuse CAD compared to focal CAD (p=0.001) and patients without CAD (p=0.006). On multivariate regression MPAs with Mon2 independently predicted diffuse CAD (odds ratio 1.10, 95% confidence interval 1.02-1.19, p=0.01) and correlated negatively with endothelium-dependent microvascular vasodilation (r= -0.37, p=0.008), an association which persisted after adjustment for covariates. Longitudinal observation confirmed persistence of an inverse relationship between MPAs with Mon2 and endothelial-dependent microvascular function.CONCLUSION: MPAs with Mon2 are increased in patients with diffuse CAD and therefore could represent an important contributor to accelerated coronary atherosclerotic progression by a mechanism involving microvascular endothelial dysfunction. This article is protected by copyright. All rights reserved.
KW - diffuse coronary artery disease
KW - microvascular function
KW - monocyte-platelet aggregates
KW - Leukocytes, Mononuclear/physiology
KW - Blood Platelets/physiology
KW - Humans
KW - Middle Aged
KW - Male
KW - Laser-Doppler Flowmetry
KW - Microcirculation/physiology
KW - Microvessels/physiology
KW - Disease Progression
KW - Endothelium, Vascular/physiology
KW - Forearm/blood supply
KW - Platelet Aggregation/physiology
KW - Female
KW - Coronary Artery Disease/blood
UR - http://www.scopus.com/inward/record.url?scp=85043318565&partnerID=8YFLogxK
U2 - 10.1111/eci.12911
DO - 10.1111/eci.12911
M3 - Journal article
C2 - 29423944
SN - 0014-2972
VL - 48
SP - e12911
JO - European Journal of Clinical Investigation
JF - European Journal of Clinical Investigation
IS - 5
M1 - e12911
ER -