Aortic VCAM‐1: an early marker of vascular inflammation in collagen‐induced arthritis

Abstract

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). There are limited experimental data on vascular involvement in arthritis models. To study the link between CVD and inflammation in RA, we developed a model of vascular dysfunction and articular inflammation by collagen‐induced arthritis (CIA) in C57Bl/6 (B6) mice. We studied the expression of vascular inflammatory markers in CIA with and without concomitant hyperlipidic diet (HD). Collagen‐induced arthritis was induced with intradermal injection of chicken type‐II collagen followed by a boost 21 days later. Mice with and without CIA were fed a standard diet or an HD for 12 weeks starting from the day of the boost. Arthritis severity was evaluated with a validated clinical score. Aortic mRNA levels of vascular cell adhesion molecule‐1 (VCAM‐1), inducible nitric oxide synthase (iNOS) and interleukin‐17 were analysed by quantitative RT‐PCR. Vascular cell adhesion molecule‐1 localization in the aortic sinus was determined by immunohistochemistry. Atherosclerotic plaque presence was assessed in aortas. Collagen‐induced arthritis was associated with increased expression of VCAM‐1, independent of diet. VCAM‐1 overexpression was detectable as early as 4 weeks after collagen immunization and persisted after 15 weeks. The HD induced atheroma plaque formation and aortic iNOS expression regardless of CIA. Concomitant CIA and HD had no additive effect on atheroma or VCAM‐1 or iNOS expression. CIA and an HD diet induced a distinct and independent expression of large‐vessel inflammation markers in B6 mice. This model may be relevant for the study of CVD in RA.

Toll‐Like Receptor 4–Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression

“…After CIA mice were sacrificed, the synovial tissue near the patella of the CIA mouse was collected to extract the total RNA for reverse transcription PCR (RT-PCR) and quantitative PCR. The CD11c+ cell suspension was counted and RNA was extracted, and the expression of TLR receptors was determined by quantitative RT-PCR [17]. Primer sequences and conditions for PCR were from the paper described previously [7].…”

“…The PCR was initiated for 2 min at 95°C, continued with 40 cycles of 10 sec at 95°C and 40 sec at 60°C. The fold change in expression of each gene was calculated using the ΔΔCt method, with the housekeeping gene β -actin mRNA as an internal control [17].…”

The VEGFA156b isoform is dysregulated in senescent endothelial cells and may be associated with prevalent and incident coronary heart disease

“…FN1 encodes fibronectin, an important component of the extracellular matrix, isoforms of which have been implicated in thrombosis [31]. VCAM and ICAM encode cellular adhesion molecules, and have been implicated in vascular inflammation, coronary flow and stroke [32–34]. ENG encodes endoglin, a molecule with roles in cardiac remodelling, which has been implicated in myocardial fibrosis [35].…”

Induced, but not natural, regulatory T cells retain phenotype and function following exposure to inflamed synovial fibroblasts

“…Another notable observation was that the iT reg , but not nT reg , subset directly targeted inflamed SFs. TNF, IL-1, and IL-6 promote the migration and invasion of SFs, and VCAM-1 sustains the synovial inflammation and promotes adherence of peripheral blood cells to endothelial cells (40). RANKL is a critical determinant of osteoclastogenesis (21).…”