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

• Published in: Scientific reports Vol. 9; no. 1; p. 4337
• Main Authors: Thiem, Kathrin, Hoeke, Geerte, van den Berg, Susan, Hijmans, Anneke, Jacobs, Cor W. M., Zhou, Enchen, Mol, Isabel M., Mouktaroudi, Maria, Bussink, Johan, Kanneganti, Thirumala D., Lutgens, Esther, Stienstra, Rinke, Tack, Cees J., Netea, Mihai G., Rensen, Patrick C. N., Berbée, Jimmy F. P., van Diepen, Janna A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.03.2019; Nature Publishing Group
• Subjects: 13/21; 13/31; 13/51; 14; 14/1; 38; 38/77; 38/90; 631/250/2504/342; 64; 692/699/75/593/2100; 82; Animals; Arteriosclerosis; Atherosclerosis; Bone composition; Bone marrow; Bone marrow transplantation; CARD Signaling Adaptor Proteins - genetics; Caspase; Chair Nutrition Metabolism and Genomics; Cholesterol; Clonal deletion; Cytokines; Hematopoietic System - metabolism; HNE Nutrition, Metabolism and Genomics; HNE Voeding, Metabolisme en Genomics; Humanities and Social Sciences; Hyperlipidemias - blood; Hyperlipidemias - pathology; Inflammation; Lectins, C-Type - genetics; Lesions; Low density lipoprotein receptors; Macrophages; Mice; Mice, Knockout; Monocyte chemoattractant protein 1; multidisciplinary; Nutrition, Metabolism and Genomics; Pattern recognition; Pattern recognition receptors; Peritoneum; Plaque, Atherosclerotic - pathology; Plaque, Atherosclerotic - prevention & control; Receptor density; Rodents; Science; Science (multidisciplinary); Transcription activation; Voeding, Metabolisme en Genomica
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-40663-x

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.