Cardiac Immune Cells in SKG Mice with Inflammatory Arthritis before and after Myocardial Infarction

Christine Hsieh¹, Isabella Imhof², Luyi Li³, Erene Niemi¹, Matthew Bell¹, Joel Karliner⁴ and Mary Nakamura⁵, ¹Medicine, SFVA/UCSF, San Francisco, CA, ²Medicine, SFVA/NCIRE, San Francisco, CA, ³SFVA/UCSF, San Francisco, CA, ⁴Medicine, SFVA/UCSF, San, CA, ⁵Department of Medicine, Division of Rheumatology, UCSF/SFVA, San Francisco, CA

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Cardiovascular disease, innate immunity, macrophages and rheumatoid arthritis (RA)

Session Information

Date: Sunday, November 5, 2017

Title: Rheumatoid Arthritis – Animal Models Poster I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose:

Cardiovascular disease is a major cause of morbidity and mortality in patients with rheumatoid arthritis (RA). RA patients have an increased incidence of both myocardial infarction (MI) and congestive heart failure. Cardiac immune cells have been demonstrated to influence cardiac remodeling post infarction and our study examined the effect of inflammatory arthritis on cardiac immune cells using a mouse model of myocardial infarction in SKG mice, a model of inflammatory arthritis.

Methods:

Arthritis was induced in female SKG mice (BALB/c ZAP-70^W163C-mutants) with a single injection of zymosan at 12 weeks age and were examined after development of athritis at 4 weeks. Wild type Balb/c mice, SKG mice, and SKG mice with arthritis (4 weeks post-zymosan) with MI underwent permanent left anterior descending coronary artery ligation. Cardiac leukocytes were evaluated at day 1 and 6 post-infarction, following harvest with cardiac perfusion, disaggregation of the heart, collagenase digestion, cellular isolation and antibody staining for multicolor flow cytometry. Cells were analyzed using a FACS Aria and FlowJo software (hearts were analyzed individually, 5 mice per group) using lineage markers (CD90/CD19/NK1.1/Ly-6G)to evaluate T cells, B cells, NK cells, granulocytes and myeloid markers CD11b, F4/80, Ly-6C.

Results:

Hearts isolated from SKG mice without arthritis showed a slight increase in the number of cardiac neutrophils compared with wild type Balb/c, that was increased by 3-4 fold in SKG mice with arthritis. At baseline SKG mice with arthritis also had a 2-3 fold increase in inflammatory macrophages (Ly6C+) compared with either SKG or Balb/c mice. Hearts isolated from SKG mice with arthritis 1 day post MI, showed a 5-6 fold increase in Ly6G+ cells (neutrophils) and Ly6C+/CD11b (monocyte/macrophages) cells compared to the basal numbers seen in hearts isolated from wild-type Balb/c mice. At day 6, SKG mice and SKG mice with arthritis both showed a persistent increase in Ly-6C+ macrophages compared with the decrease in these cells observed in Balc/c mice at the same time point. Functional outcomes post-MI correlated with these changes are currently being evaluated.

Conclusion:

We found that inflammatory arthritis induces changes in the number and phenotype of cardiac immune cells in mice both before and after myocardial infarction which likely influences cardiac repair and ventricular remodeling post-MI contibuting to detrimental cardiac outcomes with inflammatory arthritis.

Disclosure: C. Hsieh, None; I. Imhof, None; L. Li, None; E. Niemi, None; M. Bell, None; J. Karliner, None; M. Nakamura, None.

To cite this abstract in AMA style:

Hsieh C, Imhof I, Li L, Niemi E, Bell M, Karliner J, Nakamura M. Cardiac Immune Cells in SKG Mice with Inflammatory Arthritis before and after Myocardial Infarction [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/cardiac-immune-cells-in-skg-mice-with-inflammatory-arthritis-before-and-after-myocardial-infarction/. Accessed .

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