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A10.11 Non-canonical nf-κb signalling in microvessels of atherosclerotic lesions in coronary arteries is associated with inflammatory cell infiltration and myocardial infarction
  1. CX Maracle1,2,
  2. R Agca3,4,
  3. B Helder1,2,
  4. HWM Niessen3,4,
  5. M Nurmohamed3,4,
  6. SW Tas1,2
  1. 1Amsterdam Rheumatology and Immunology Center – Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  2. 2Laboratory for Experimental Immunology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
  3. 3Amsterdam Rheumatology and Immunology Center – READE, Amsterdam, The Netherlands
  4. 4Amsterdam Rheumatology and Immunology Center – VUMC, Amsterdam, The Netherlands

Abstract

Background and objective Patients with chronic inflammatory diseases (CID) have higher risk of developing cardiovascular disease which may be in part due to increased systemic inflammatory burden. In atherosclerosis, extensive neovascularization is associated with plaque instability and increased chance of myocardial infarction (MI). We have established that non-canonical NF-κB signalling, and its central regulator NF-κB inducing kinase (NIK) in endothelial cells (EC) contributes to angiogenesis in synovial tissue of patients with various types of arthritis. Thus, we hypothesised that NIK+ EC may also contribute to neovascularization in atherosclerotic lesions.

Methods Atherosclerotic lesions from 11 individuals with CID and 11 matched controls, isolated from parts of the coronary artery implicated in MI (CA+) or not (CA-), were immunohistochemically stained with antibodies against NIK, CD31/34 (EC), myeloperoxidase (neutrophils), CD45 (lymphocytes), CD68 (macrophages) and tryptase (mast cells). NIK vessel density (NIK+VD) and immune cell density (ICD) were subsequently calculated.

Results NIK+EC were present in atherosclerotic lesions of all coronary arteries. NIK+VD significantly correlated with ICD of all characterised immune cells: leukocytes (r = 0.5227; p < 0.0001), macrophages (r = 0.3397, p < 0.0001), mast cells (r = 0.4205, p < 0.0001) and neutrophils (r = 0.2129, p = 0.0016). No significant differences were found in NIK+VD in CID patients versus healthy, however, influx of leukocytes and macrophages per NIK+ microvessel was significantly higher in CID lesions. Increased NIK+ microvessels were also noted in CA+ as compared to CA- tissues (p = 0.0139) in both healthy and CID patients.

Conclusions NIK+ microvesselsare present inhigh numbers in atherosclerotic lesions and are strongly associated with the influx of inflammatory cells. Systemic inflammation is not a prerequisite for activation of this pathway in EC in atherosclerotic lesions, but our findings suggest that non-canonical NF-κB signalling is more pronounced in patients with CID resulting in the attraction of more immune cells that may further enhance progression of atherosclerotic lesions. Since activation of the non-canonical NF-κB pathway in EC induces angiogenesis and NIK+ vessels are increased in coronary arteries associated with MI, non-canonical NF-κB signalling in EC may drive neovascularization and plaque instability, thus increasing the chance of developing a (fatal) MI.

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