Deletion of haematopoietic Dectin-2 or CARD9 does not protect from atherosclerosis development under hyperglycaemic conditions.

Abstract

BACKGROUND:

C-type lectin receptors, including Dectin-2, are pattern recognition receptors on monocytes and macrophages that mainly recognize sugars and sugar-like structures present on fungi. Activation of C-type lectin receptors induces downstream CARD9 signalling, leading to the production of cytokines. We hypothesized that under hyperglycaemic conditions, as is the case in diabetes mellitus, glycosylated protein (sugar-like) structures activate C-type lectin receptors, leading to immune cell activation and increased atherosclerosis development.

METHODS:

Low-density lipoprotein receptor-deficient mice were lethally irradiated and transplanted with bone marrow from control wild-type, Dectin-2-/- or Card9-/- mice. After 6 weeks of recovery, mice received streptozotocin injections (50 mg/g BW; 5 days) to induce hyperglycaemia. After an additional 2 weeks, mice were fed a Western-type diet (0.1% cholesterol) for 10 weeks.

RESULTS AND CONCLUSION:

Deletion of haematopoietic Dectin-2 reduced the number of circulating Ly6Chi monocytes, increased pro-inflammatory cytokine production, but did not affect atherosclerosis development. Deletion of haematopoietic CARD9 tended to reduce macrophage and collagen content in atherosclerotic lesions, again without influencing the lesion size. Deletion of haematopoietic Dectin-2 did not influence atherosclerosis development under hyperglycaemic conditions, despite some minor effects on inflammation. Deletion of haematopoietic CARD9 induced minor alterations in plaque composition under hyperglycaemic conditions, without affecting lesion size.

• Authors: Kathrin Thiem, Geerte Hoeke, Enchen Zhou, Anneke Hijmans, Tom Houben, Margien G Boels, Isabel M Mol, Esther Lutgens, Ronit Shiri-Sverdlov, Johan Bussink, Thirumala D Kanneganti, Mariëtte R Boon, Rinke Stienstra, Cees J Tack, Patrick Cn Rensen, Mihai G Netea, Jimmy Fp Berbée, Janna A van Diepen
• Journal: Diabetes & vascular disease research (Diab Vasc Dis Res) 2020 Jan-Feb Vol. 17 Issue 1 Pg. 1479164119892140 ISSN: 1752-8984 [Electronic] England
• PMID: 31868000 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Ly
• Biomarkers
• Blood Glucose
• CARD Signaling Adaptor Proteins
• Card9 protein, mouse
• Cytokines
• Lectins, C-Type
• Ly-6C antigen, mouse
• Receptors, LDL
• dectin-2, mouse
• Collagen

Topics

• Animals
• Antigens, Ly (metabolism)
• Aorta (metabolism, pathology)
• Aortic Diseases (etiology, genetics, metabolism, pathology)
• Atherosclerosis (etiology, genetics, metabolism, pathology)
• Biomarkers (blood)
• Blood Glucose (metabolism)
• Bone Marrow Transplantation
• CARD Signaling Adaptor Proteins (deficiency, genetics)
• Cells, Cultured
• Collagen (metabolism)
• Cytokines (metabolism)
• Diabetes Mellitus, Experimental (blood, complications)
• Diet, Western
• Gene Deletion
• Genetic Predisposition to Disease
• Hematopoietic Stem Cells (metabolism)
• Lectins, C-Type (deficiency, genetics)
• Macrophages, Peritoneal (metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Monocytes (metabolism, pathology)
• Plaque, Atherosclerotic
• Receptors, LDL (deficiency, genetics)