Mast cells participate in smooth muscle cell reprogramming and atherosclerotic plaque calcification

被引：9

作者：

Skenteris, Nikolaos T. ^{[1
,2
,3
,4
]}

Hemme, Esmeralda ^{[5
]}

Delfos, Lucie ^{[5
]}

Karadimou, Glykeria ^{[2
,3
]}

Karlof, Eva ^{[2
,3
]}

Lengquist, Mariette ^{[2
,3
]}

Kronqvist, Malin ^{[2
,3
]}

Zhang, Xiang ^{[2
,3
]}

Maegdefessel, Lars ^{[1
,6
]}

Schurgers, Leon J. ^{[7
,8
,9
]}

Arnardottir, Hildur ^{[1
]}

Biessen, Erik A. L. ^{[4
]}

Bot, Ilze ^{[5
]}

Matic, Ljubica ^{[2
,3
,10
]}

机构：

[1] Karolinska Inst, Dept Med, Cardiovasc Med, Stockholm, Sweden

[2] Karolinska Inst, Vasc Surg, Dept Mol Med & Surg, Stockholm, Sweden

[3] Karolinska Univ Hosp, Stockholm, Sweden

[4] Maastricht Univ Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Dept Pathol, Maastricht, Netherlands

[5] Leiden Univ, Leiden Acad Ctr Drug Res, Div BioTherapeut, Leiden, Netherlands

[6] Tech Univ Munich, Dept Vasc & Endovasc Surg, Klinikum Rechts Isar, Munich, Germany

[7] Maastricht Univ, Sch Cardiovasc Dis, Dept Biochem, Maastricht, Netherlands

[8] Maastricht Univ, Sch Cardiovasc Dis, CARIM, Maastricht, Netherlands

[9] Rhein Westfal TH Aachen, Inst Expt Med & Syst Biol, Aachen, Germany

[10] Karolinska Inst, Dept Mol Med & Surg, Div Vasc Surg, BioClinicum J8-20, SE-17176 Stockholm, Sweden

来源：

VASCULAR PHARMACOLOGY | 2023年 / 150卷

基金：

瑞典研究理事会;

关键词：

Atherosclerotic plaques; Mast cells; Smooth muscle cells; Intimal calcification; Biobank of Karolinska endarterectomy (BiKE); MYOCARDIAL-INFARCTION; SHOULDER REGION; DOWN-REGULATION; UP-REGULATION; INFLAMMATION; EXPRESSION; STENOSIS; ENDARTERECTOMY; TRANSITION; TRYPTASE;

D O I：

10.1016/j.vph.2023.107167

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Calcification, a key feature of advanced human atherosclerosis, is positively associated with vascular disease burden and adverse events. We showed that macrocalcification can be a stabilizing factor for carotid plaque molecular biology, due to inverse association with immune processes. Mast cells (MCs) are important contributors to plaque instability, but their relationship with macrocalcification is unexplored. With a hypothesis that MC activation negatively associates with carotid plaque macrocalcification, we aimed to investigate the link between MCs and carotid plaque vulnerability, and study MC role in plaque calcification via smooth muscle cells (SMCs).Methods: Pre-operative computed tomography angiographies of patients (n = 40) undergoing surgery for carotid stenosis were used to characterize plaque morphology. Plaque microarrays (n = 40 and n = 126) were used for bioinformatic deconvolution of immune cell populations. Tissue microarrays (n = 103) were used to histologi-cally validate the contribution of activated and resting MCs in plaques. Results: Activated MCs and their typical markers were negatively correlated with macrocalcification. The ratio of activated vs. resting MCs was increased in low-calcified plaques from symptomatic patients. There was no modulating effect of medication on MC ratios. In vitro experiments showed that SMC calcification attenuated MC activation, while both active and resting MCs stimulated SMC calcification and induced dedifferentiation towards a pro-inflammatory-, osteochondrocyte-like phenotype, without modulating their migro-proliferative function.Conclusions: Integrative analyses from human plaques showed that MC activation is inversely associated with macrocalcification and positively with parameters of plaque vulnerability. Mechanistically, MCs induce SMC osteogenic reprograming, while matrix calcification in turn attenuates MC activation, offering new therapeutic avenues for exploration.

引用

页数：13

共 75 条

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