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.
引用
收藏
页码:27 / 41
页数:15
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