Defective cholesterol metabolism in haematopoietic stem cells promotes monocyte-driven atherosclerosis in rheumatoid arthritis
Authors' conclusion
Rheumatoid arthritis impairs atherosclerotic regression and alters progression, which is associated with an expansion of myeloid cells and disturbed cellular cholesterol handling, independent of plasma cholesterol levels. Infusion of rHDL prevented enhanced myelopoiesis and monocyte entry into lesions.
Study context
- Population
- Mouse models of rheumatoid arthritis (RA); RA patients
- Comparison
- Arthritic vs non-arthritic mice; Reconstituted high-density lipoprotein (rHDL) infusion in progression model
- Outcome
- Atherosclerotic lesion regression or progression in relation to circulating myeloid cells
Methodological detailstwo mouse models of RA, regression and progression models
- Two mouse models of RA
- Regression and progression models
Main finding
As reported in the abstract
- Monocytosis, neutrophilia and thrombocytosis in two mouse models of RA, due to enhanced HSPC proliferation in bone marrow and spleen
- HSPC expansion associated with increased cholesterol content, due to down-regulation of cholesterol efflux genes Apoe, Abca1 and Abcg1; enhanced expression of key myeloid promoting growth factor receptors
- Systemic inflammation caused defective cellular cholesterol metabolism
- Increased myeloid cells in RA mice associated with significant impairment in lesion regression, despite cholesterol levels equivalent to non-arthritic mice
- Lesions from arthritic mice less stable: increased immune cell infiltration, lipid accumulation, decreased collagen formation
- Progression model: monocytosis, enhanced monocyte recruitment to lesions, increased plaque macrophages; reversed with rHDL
- RA patients: expanded CD16+ monocyte subsets and down-regulation of ABCA1 and ABCG1
Original publication
Defective cholesterol metabolism in haematopoietic stem cells promotes monocyte-driven atherosclerosis in rheumatoid arthritis. Eur Heart J. Published 21 March 2018. doi:10.
Summarised from the published abstract; every number is checked against it