ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1405

Expression Of High Mobility Group Protein B1 and Its Receptors In Heart Of Patients With Coronary Artery Disease With and Without Inflammatory Rheumatic Disease: A Biopsy Study

Mei Zong1, Ivana Hollan2, Huiyuan Xiao3, Cecilia Grundtman4, Eva Lindroos5, Helena E. Harris6, Knut MIkkelsen7, Stein E. Rynning7, Sven M. Almdahl8 and Ingrid E. Lundberg9, 1Rheumatology Unit, Department of Medicine, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden, 2Rheumatology, Lillehammer Hospital for Rheumatic Diseases, Lillehammer, Norway, 3University of Oxford, Oxford, United Kingdom, 4Innsbruck Medical University, Innsbruck, Austria, 5Department of Medicine, Rheumatology Unit, Karolinska University Hospital in Solna, Karolinska Institutet, Stockholm, Sweden., Stockholm, Sweden, 6Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden, 7Feiring Heart Clinic, Feiring, Norway, 8Cardiothoracic surgery, University Hospital of North Norway, Tromsø, Norway, 9Rheumatology Unit, Karolinska University Hospital, Solna, Karolinska Institutet, Stockholm, Sweden

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose:

Patients with inflammatory rheumatic diseases (IRD) have increased risk of morbidity and mortality in coronary artery disease (CAD) compared to the general population. High mobility group protein B1 (HMGB1) is an alarmin that can drive the pathogenesis of IRD when it is released from nuclei. Recently it was also shown that HMGB1 can mediate myocardial dysfunction in rat. In this study, we aimed to investigate whether and how HMGB1 and its signal-mediated receptors are expressed in heart muscle tissues of humans with CAD with or without IRD.

Methods:

We examined myocardial specimens from the right atria (1.5×2.0mm) taken during coronary artery bypass grafting from 18 patients with CAD included in Feiring Heart Biopsy Study between 2001 and 2004. Among them, 10 patients had an IRD (IRD group) and 8 patients were without IRD (control group). The IRD group comprised of 5 patients with rheumatoid arthritis, 2 with polymyalgia rheumatica, 1 with psoriasis arthritis, 1 with temporal arteritis and 1 patient with ankylosing spondylitis. The heart samples were snap-frozen and stored at -80°C until they were cryostat-sectioned and stained by immunohistochemistry using the antibodies specific for HMGB1 and its three most well-known receptors: Toll-like receptor (TLR) 2, TLR4 and receptor for advanced glycation end products (RAGE). The cytosol HMGB1 staining was described as weak (+) and strong (++) which was scored without knowing the identity of the patients.

Results:

In the control group, HMGB1 was localized to the nuclei of cardiomyocytes in 7 out of 8 patients, while in one patient it was also detected in the cytoplasm weakly (+). In contrast, in the IRD group, HMGB1 was strongly expressed in the cytosol of the cardiomyocytes in 6 out of 10 patients (++), and weakly expressed in cytosol in the remaining 4 patients (+). For the receptors, RAGE and TLR4 displayed a general expression in the cardiomyocytes mainly localized to the cytosol, while TLR2 was detectable in the cytosol of occasional cardiomyocytes.

Conclusion:

HMGB1 and its receptors are expressed in the cardiomyocytes of patients with CAD. However, the HMGB1-signalling pathways may get a “better” chance to be activated in the patients with IRD as HMGB1 was detected with a more pronounced extranuclear staining pattern compared to the non-IRD patients. Therefore, targeting HMGB1 therapy in the future may protect the patients with IRD from developing severe cardiovascular diseases.

Disclosure:

M. Zong,
None;

I. Hollan,
None;

H. Xiao,
None;

C. Grundtman,
None;

E. Lindroos,
None;

H. E. Harris,
None;

K. MIkkelsen,
None;

S. E. Rynning,
None;

S. M. Almdahl,
None;

I. E. Lundberg,

BMS,

2,

Novartis Pharmaceutical Corporation,

5.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/expression-of-high-mobility-group-protein-b1-and-its-receptors-in-heart-of-patients-with-coronary-artery-disease-with-and-without-inflammatory-rheumatic-disease-a-biopsy-study/