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Sci Rep. 2019 Mar 13;9(1):4337. doi: 10.1038/s41598-019-40663-x.

Deletion of hematopoietic Dectin-2 or CARD9 does not protect against atherosclerotic plaque formation in hyperlipidemic mice.

Author information

1
Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands. kathrin.thiem@radboudumc.nl.
2
Department of Medicine, Div. of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands.
3
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
4
Department of Medical Biochemistry, Div. of Experimental Vascular Biology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
5
Department of Internal Medicine and Radboud Institute for Molecular Life Sciences, Radboud university medical center, Nijmegen, The Netherlands.
6
Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
7
Dept. of Radiation Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
8
Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
9
Institute for Cardiovascular Prevention, Ludwig Maximilians University of Munich, Munich, Germany.
10
Div. of Human Nutrition, Wageningen University, Wageningen, The Netherlands.
11
Department for Genomics & Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, Bonn, Germany.

Abstract

Inflammatory reactions activated by pattern recognition receptors (PRRs) on the membrane of innate immune cells play an important role in atherosclerosis. Whether the PRRs of the C-type lectin receptor (CLR) family including Dectin-2 may be involved in the pathogenesis of atherosclerosis remains largely unknown. Recently, the CLR-adaptor molecule caspase recruitment domain family member 9 (CARD9) has been suggested to play a role in cardiovascular pathologies as it provides the link between CLR activation and transcription of inflammatory cytokines as well as immune cell recruitment. We therefore evaluated whether hematopoietic deletion of Dectin-2 or CARD9 reduces inflammation and atherosclerosis development. Low-density lipoprotein receptor (Ldlr)-knockout mice were transplanted with bone marrow from wild-type, Dectin-2- or Card9-knockout mice and fed a Western-type diet containing 0.1% (w/w) cholesterol. After 10 weeks, lipid and inflammatory parameters were measured and atherosclerosis development was determined. Deletion of hematopoietic Dectin-2 or CARD9 did not influence plasma triglyceride and cholesterol levels. Deletion of hematopoietic Dectin-2 did not affect atherosclerotic lesion area, immune cell composition, ex vivo cytokine secretion by peritoneal cells or bone marrow derived macrophages. Unexpectedly, deletion of hematopoietic CARD9 increased atherosclerotic lesion formation and lesion severity. Deletion of hematopoietic CARD9 did also not influence circulating immune cell composition and peripheral cytokine secretion. Besides a tendency to a reduced macrophage content within these lesions, plasma MCP-1 levels decreased upon WTD feeding. Deletion of hematopoietic Dectin-2 did not influence atherosclerosis development in hyperlipidemic mice. The absence of CARD9 unexpectedly increased atherosclerotic lesion size and severity, suggesting that the presence of CARD9 may protect against initiation of atherosclerosis development.

PMID:
30867470
DOI:
10.1038/s41598-019-40663-x
Free PMC Article

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