Sime Katie, Choy Ernest H, Williams Anwen S
a Division of Infection and Immunity, Department of Rheumatology , Cardiff University School of Medicine , Cardiff , United Kingdom.
b The Cardiff Regional Experimental Arthritis Treatment and Evaluation Centre (CREATE Centre) , Cardiff University School of Medicine , Cardiff , United Kingdom.
Adipocyte. 2017 Apr 3;6(2):87-101. doi: 10.1080/21623945.2017.1295174. Epub 2017 Feb 21.
The physiologic function of adipose tissue is altered by the host's inflammatory response; the implications for maintaining human health and regulating inflammation-associated disease progression are ill defined. However, this cannot be investigated in humans, therefore the use of animal models is required. With the aim to determine morphological and molecular alterations to perivascular and organ-associated adipose tissues during inflammatory arthritis, collagen-induced arthritis (CIA) was established in male DBA/1 mice. Emerging evidence from this study signposts CIA in the DBA/1 mouse as a model that is relevant to study the development and treatment of early cardiovascular pathology associated with inflammatory arthritis. Here, we show global morphological changes in adipose tissue and the thoracic aorta in animals induced with CIA compared with the non-immunized controls. In CIA, we concluded that the increased cell count in PVAT was, at least in part, caused by an ingress and/or expansion of macrophages that had a mixed phenotype. A substantial increase of galectin-3 was expressed in PVAT from mice with CIA. Galectin-3 is elevated in the blood of patients with CVDs, however, it has never before been measured in PVAT in rodents or humans. Here, PVAT-associated galectin-3 is identified as a potential biomarker for detecting early vascular pathology in CIA and a promising candidate for translation to RA.
脂肪组织的生理功能会因宿主的炎症反应而改变;其对维持人类健康和调节炎症相关疾病进展的影响尚不明确。然而,这无法在人体中进行研究,因此需要使用动物模型。为了确定炎症性关节炎期间血管周围和器官相关脂肪组织的形态和分子变化,在雄性DBA/1小鼠中建立了胶原诱导性关节炎(CIA)模型。这项研究的新证据表明,DBA/1小鼠中的CIA是一种与研究炎症性关节炎相关的早期心血管病理发展和治疗相关的模型。在这里,我们展示了与未免疫对照组相比,CIA诱导的动物脂肪组织和胸主动脉的整体形态变化。在CIA中,我们得出结论,PVAT中细胞数量的增加至少部分是由具有混合表型的巨噬细胞的侵入和/或扩张引起的。CIA小鼠的PVAT中半乳糖凝集素-3的表达大幅增加。半乳糖凝集素-3在心血管疾病患者的血液中升高,然而,此前从未在啮齿动物或人类的PVAT中进行过测量。在这里,PVAT相关的半乳糖凝集素-3被确定为检测CIA早期血管病理的潜在生物标志物,也是转化为类风湿性关节炎的有希望的候选物。