Psoriasis and cardiovascular risk factors: increased serum myeloperoxidase and corresponding immunocellular overexpression by Cd11b(+) CD68(+) macrophages in skin lesions

Abstract

Background: Recent studies report independent associations between psoriasis, cardiovascular (CV) events and risk factors. Blood Myeloperoxidase (MPO) from activated myeloid cells is associated with CV risk mainly through lipid oxidation, induction of endothelial dysfunction and release of IL-12 from macrophages.

Objectives: To elucidate associations between psoriasis and conventional CV risk factors.

Methods: We performed a cross-sectional study of 100 psoriasis patients and 53 controls, group matched on age, gender and body mass index, to assess levels of MPO in serum, as well as immunohistochemical staining from psoriasis skin lesions, psoriasis uninvolved skin, and normal skin.

Results: Although the groups did not differ on waist circumference, glucose, cholesterol, triglycerides, creatinine or personal history of CV events, psoriasis patients had significantly higher waist-to-hip ratios, blood pressures, proportion of current smokers, and lower high density lipoprotein level than controls. Serum MPO level was elevated 2.5 fold (P<0.001) in psoriasis patients, even after adjusting for the CV risk factors on which the groups differed. MPO did correlate with coronary artery calcification, carotid plaque, carotid intima media thickness and flow mediated dilation, but did not correlate with psoriasis severity. However, MPO was highly expressed in lesional psoriatic skin and colocalized predominantly with CD45(+) CD11b(+) leukocytes. CD11b(+) cell density correlated with circulation MPO levels.

Conclusion: Lesional skin CD11b(+) leukocytes activated to generate MPO may contribute to serum levels of MPO. Lesional CD11b(+) cell activity may be an alternative measure of disease burden to PASI that underlies the MPO biomarker for systemic inflammation related to Cardiovascular Disease.

Keywords: Myeloperoxidase; cardiovascular disease; immunofluorescence; immunohistochemistry; psoriasis.

Figure 1

MPO is highly expressed in lesional psoriatic skin. 8 μm sections of frozen human skin biopsies were labeled with MPO antibody (red) and the nuclear stain Hoechst 33253 (blue). MPO was detectable by confocal microscopy in lesional psoriatic skin (A) primarily in the dermo-epidermal junction and papillary dermis, and was minimal in non-lesional psoriatic skin (B) and non-psoriatic skin (C). Scale bar = 50 μm. Representative image of n>7 patients.

Figure 2

MPO positive cells co-localize with CD45⁺ cells within lesional psoriatic skin. 8 μm sections of frozen human skin biopsies were labeled with MPO antibody (red, A), CD45 antibody (green, B) and the nuclear stain Hoechst 33253 (blue). MPO was detectable by confocal microscopy mainly in the dermo-epidermal junction and papillary dermis, co-localized with CD45⁺ lymphocytes (white arrows, C). Scale bar = 50 μm. Representative image of n>7 patients.

Figure 3

Neutrophil elastase and MPO expression patterns are distinct in serial tissue sections from lesional psoriatic skin. 8 μm serial sections of frozen human skin biopsies were labeled with either MPO (A) or neutrophil elastase (B) and counterstained with hematoxylin. Scale bar = 100 μm. Representative image of n>3 patients.

Figure 4

A subset of MPO⁺ cells in lesional psoriatic skin express mature macrophage-specific markers CD68 and HAM56. 8 μm sections of frozen human skin biopsies were labeled with MPO antibody (red, A and D), CD68 (green, B) or HAM56 (green, E) and the nuclear stain Hoechst 33253 (blue) in lesional psoriatic skin. Double labeling was detected by confocal microscopy. Cells that co-localized for MPO and either CD68 (C) or Ham56 (F) are indicated (white arrows). Scale bar = 50 μm. Representative image of n>3 patients.

Figure 5

Lesional psoriatic MPO⁺ cells express CD11b. 8 μm sections of frozen human skin biopsies were labeled with MPO antibody (green, A), CD11b (red, B) and the nuclear stain Hoechst 33253 (blue) in lesional psoriatic skin. Double staining was detected by confocal microscopy and localized primarily to the dermo-epidermal junction and papillary dermis. Co-localized (MPO⁺ CD11b⁺) cells are indicated (white arrows, C). Scale bar = 50 μm. Representative image of n>9 patients.

Figure 6

Serum MPO correlates with increased CD11b⁺ cells within high PASI patients. 8 μm sections of frozen lesional psoriatic skin of patients with PASI>15 and above were labeled and counted for CD11b⁺ cells and the MPO serum levels were found to correlate with the CD11b index (CD11b⁺ cells divided by μ² ) using a non-parametric Spearman correlation (n=8).