6
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Protective effect of hydroxychloroquine on rheumatoid arthritis‐associated atherosclerosis

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease. We examined the effect of gut microbiota in a mouse model of RA that develops atherosclerosis.

          Methods

          We created three groups of K/BxN female mice that were positive for the anti‐glucose‐6‐phosphate isomerase (GPI) antibody: control diet (CD), high fat diet (HFD), and HFD with hydroxychloroquine (HFD + HCQ). Serological tests were used to detect the serum levels of total cholesterol (TCHO), low‐density lipoprotein cholesterol (LDL‐C), triglyceride (TG), high‐density lipoprotein cholesterol (HDL‐C), anti‐GPI antibody titers, and serum cytokines. Atherosclerotic plaque was determined by histological analysis, and gut microbiota were determined by 16sV4 sequencing.

          Results

          Relative to mice given the CD, those receiving the HFD had increased serum levels of LDL‐C, TCHO, and TG, decreased serum levels of HDL‐C, increased atherosclerotic lesions in the aortic root, and altered gut microbiota. Addition of HCQ to HFD decreased the serum levels of LDL‐C, TCHO, and TG, increased serum levels of HDL‐C, and decreased the atherosclerotic lesions in the aortic root. Mice receiving HFD + HCQ also had the greatest bacterial diversity among the three experimental groups. Moreover, HCQ treatment significantly increased the abundance of Akkermansia and Parabacteroides, and decreased the abundance of Clostridium sensu stricto cluster 1, and therefore may be responsible for the reduced RA‐associated atherosclerosis and dyslipidemia.

          Conclusion

          Our mouse model of RA indicated that HFD increased ankle width and aggravated atherosclerosis and dyslipidemia, and that HCQ alleviated the dyslipidemia and atherosclerosis, but had no effect on ankle width.

          Related collections

          Most cited references28

          • Record: found
          • Abstract: found
          • Article: not found

          Clinical efficacy and side effects of antimalarials in systemic lupus erythematosus: a systematic review.

          Antimalarial drugs (AMs), chloroquine (CQ) and hydroxychloroquine (HCQ), are frequently withdrawn in patients with lupus with either severe or remitting disease. However, additional effects beyond immunomodulation have been recently described. The aim of the present work was to analyse all the published evidence of the beneficial and adverse effects of AM therapy in systemic lupus erythematosus (SLE). A systematic review of the English literature between 1982 and 2007 was conducted using the MEDLINE and EMBASE databases. Randomised controlled trials (RCTs) and observational studies were selected. Case reports were excluded except for toxicity reports. The GRADE system was used to analyse the quality of the evidence. A total of 95 articles were included in the systematic review. High levels of evidence were found that AMs prevent lupus flares and increase long-term survival of patients with SLE; moderate evidence of protection against irreversible organ damage, thrombosis and bone mass loss. Toxicity related to AMs is infrequent, mild and usually reversible, with HCQ having a safer profile. In pregnant women, high levels of evidence were found that AMs, particularly HCQ, decrease lupus activity without harming the baby. By contrast, evidence supporting an effect on severe lupus activity, lipid levels and subclinical atherosclerosis was weak. Individual papers suggest effects in preventing the evolution from SLE-like to full-blown SLE, influencing vitamin D levels and protecting patients with lupus against cancer. Given the broad spectrum of beneficial effects and the safety profile, HCQ should be given to most patients with SLE during the whole course of the disease, irrespective of its severity, and be continued during pregnancy.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            From systemic T cell self-reactivity to organ-specific autoimmune disease via immunoglobulins.

            Rheumatoid arthritis is a common and debilitating autoimmune disease whose cause and mechanism remain a mystery. We recently described a T cell receptor transgenic mouse model that spontaneously develops a disease with most of the clinical, histological, and immunological features of rheumatoid arthritis in humans. Disease development in K/BxN mice is initiated by systemic T cell self-reactivity; it requires T cells, as expected, but B cells are also needed, more surprisingly. Here, we have identified the role of B cells as the secretion of arthritogenic immunoglobulins. We suggest that a similar scenario may unfold in some other arthritis models and in human patients, beginning with pervasive T cell autoreactivity and ending in immunoglobulin-provoked joint destruction.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Fecal microbiota in early rheumatoid arthritis.

              To compare the composition of intestinal microbiota of patients with early rheumatoid arthritis (RA) or fibromyalgia (FM), fecal samples were collected from 51 patients with RA and 50 with FM. RA patients fulfilled the RA criteria of the American College of Rheumatology, and duration of their disease was < or = 6 months. Only nonhospitalized patients from outpatient care were included. Patients having extreme diets or previous disease modifying antirheumatic drug or glucocorticoid medication were excluded, as were those taking antibiotics or having gastroenteritis for at least 2 months prior to sampling. Fecal bacterial composition was analyzed with a method based on flow cytometry, 16S rRNA hybridization, and DNA-staining. A set of 8 oligonucleotide probes was used. In comparison to patients with FM, the RA patients had significantly less bifidobacteria and bacteria of the Bacteroides-Porphyromonas-Prevotella group, Bacteroides fragilis subgroup, and Eubacterium rectale--Clostridium coccoides group. Results from the 8 probes showed a significant overall difference between the 2 patient groups, indicating widespread microbial differences. These findings support the hypothesis that intestinal microbes participate in the etiopathogenesis of RA.
                Bookmark

                Author and article information

                Contributors
                mengtao.li@cstar.org.cn
                caijun7879@126.com
                niuhaitao@cnilas.org
                Journal
                Animal Model Exp Med
                Animal Model Exp Med
                10.1002/(ISSN)2576-2095
                AME2
                Animal Models and Experimental Medicine
                John Wiley and Sons Inc. (Hoboken )
                2096-5451
                2576-2095
                19 April 2019
                June 2019
                : 2
                : 2 ( doiID: 10.1002/ame2.2019.2.issue-2 )
                : 98-106
                Affiliations
                [ 1 ] NHC Key Laboratory of Human Disease Comparative Medicine (The Institute of Laboratory Animal Sciences, CAMS&PUMC), Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases Beijing China
                [ 2 ] Department of Rheumatology, Langone Medical Center New York University New York City New York
                [ 3 ] Peking Union Medical College Hospital Beijing China
                [ 4 ] Fuwai Hospital Chinese Academy of Medical Sciences Beijing China
                Author notes
                [*] [* ] Correspondence

                Haitao Niu, NHC Key Laboratory of Human Disease Comparative Medicine (The Institute of Laboratory Animal Sciences, CAMS&PUMC), Beijing Engineering Research Center for Experimental Animal Models of Human Critical Diseases, Key Laboratory of Human Diseases Animal Model, State Administration of Traditional Chinese Medicine), Beijing, China.

                Email: niuhaitao@ 123456cnilas.org

                Mengtao Li, Peking Union Medical College Hospital, Beijing, China.

                Email: mengtao.li@ 123456cstar.org.cn

                Jun Cai, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing, China.

                Email: caijun7879@ 123456126.com

                Author information
                https://orcid.org/0000-0003-2210-2051
                Article
                AME212065
                10.1002/ame2.12065
                6600633
                31392302
                d78f0a8c-2a75-4f09-aa83-1ff8d955efdf
                © 2019 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 09 January 2019
                : 04 March 2019
                Page count
                Figures: 4, Tables: 0, Pages: 9, Words: 4839
                Funding
                Funded by: CAMS Initiative for Innovative Medicine of China
                Award ID: 2016-12M-1-006
                Funded by: National Key R&D Program of China
                Award ID: 2017YFC1103603
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                ame212065
                June 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.5 mode:remove_FC converted:01.07.2019

                atherosclerosis,autoimmunity,hydroxychloroquine,intestinal microbiota,rheumatoid arthritis

                Comments

                Comment on this article