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Effector Memory T cells Are Associated With Atherosclerosis in Humans and Animal Models
被引:139
作者:
Ammirati, Enrico
[1
,5
,6
,11
]
Cianflone, Domenico
[1
]
Vecchio, Viviana
[2
]
Banfi, Michela
[1
]
Vermi, Anna C.
De Metrio, Monica
[7
]
Grigore, Liliana
[8
,10
]
Pellegatta, Fabio
[8
]
Pirillo, Angela
Garlaschelli, Katia
Manfredi, Angelo A.
[3
,4
]
Catapano, Alberico L.
[9
,10
]
Maseri, Attilio
[11
]
Palini, Alessio G.
[2
]
Norata, Giuseppe D.
[9
]
机构:
[1] Ist Sci San Raffaele, Clin Cardiovasc Biol Ctr, I-20132 Milan, Italy
[2] Ist Sci San Raffaele, Flow Cytometry Resource Analyt Cytol Tech Applica, I-20132 Milan, Italy
[3] Ist Sci San Raffaele, Clin Immunol Unit, I-20132 Milan, Italy
[4] Univ Vita Salute San Raffaele, I-20133 Milan, Italy
[5] Osped Niguarda Ca Granda, Heart Transplantat Div, Milan, Italy
[6] Ist Ricovero & Cura Carattere Sci, Ctr Cardiol Monzino, Milan, Italy
[7] Univ Milan, Dept Cardiovasc Sci, Milan, Italy
[8] Italian Soc Study Atherosclerosis Lombardia Chapt, Bassini Hosp Cinisello Balsamo, Ctr Study Atherosclerosis, Milan, Italy
[9] Univ Milan, Dept Pharmacol Sci, Milan, Italy
[10] Multimed IRCCS, SS Giovanni Milan, Florence, Italy
[11] Heart Care Fdn, Florence, Italy
来源:
JOURNAL OF THE AMERICAN HEART ASSOCIATION
|
2012年
/
1卷
/
01期
关键词:
atherosclerosis;
C-c chemokine receptor type 7;
chemokines;
coronary artery disease;
effector memory T cells;
ACUTE CORONARY SYNDROMES;
LOW-DENSITY-LIPOPROTEIN;
ACUTE MYOCARDIAL-INFARCTION;
RECEPTOR-DEFICIENT MICE;
MONOCYTE-DERIVED CELLS;
UNSTABLE ANGINA;
IMMUNE-SYSTEM;
REDUCES ATHEROSCLEROSIS;
VASCULAR INFLAMMATION;
FLOW-CYTOMETRY;
D O I:
10.1161/JAHA.111.000125
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Background-Adaptive T-cell response is promoted during atherogenesis and results in the differentiation of naive CD4(+)T cells to effector and/or memory cells of specialized T-cell subsets. Aim of this work was to investigate the relationship between circulating CD4(+)T-cell subsets and atherosclerosis. Methods and Results-We analyzed 57 subsets of circulating CD4(+)T cells by 10-parameter/8-color polychromatic flow cytometry (markers: CD3/CD4/CD45RO/CD45RA/CCR7/CCR5/CXCR3/HLA-DR) in peripheral blood from 313 subjects derived from 2 independent cohorts. In the first cohort of subjects from a free-living population (n=183), effector memory T cells (T-EM: CD3(+)CD4(+)CD45RA(-)CD45RO(+)CCR7(-) cells) were strongly related with intima-media thickness of the common carotid artery, even after adjustment for age (r=0.27; P<0.001). Of note, a significant correlation between T-EM and low-density lipoproteins was observed. In the second cohort (n=130), T-EM levels were significantly increased in patients with chronic stable angina or acute myocardial infarction compared with controls. HLA-DR+TEM were the T-EM subpopulation with the strongest association with the atherosclerotic process (r=0.37; P<0.01). Finally, in animal models of atherosclerosis, T-EM (identified as CD4(+)CD44(+)CD62L(-)) were significantly increased in low-density lipoprotein receptor and apolipoprotein E deficient mice compared with controls and were correlated with the extent of atherosclerotic lesions in the aortic root (r=0.56; P<0.01). Conclusions-Circulating T-EM cells are associated with increased atherosclerosis and coronary artery disease in humans and in animal models and could represent a key CD4(+)T-cell subset related to the atherosclerotic process.
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页码:27 / 41
页数:15
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