Endothelial cell activation and neovascularization are prominent in dermatomyositis

Kanneboyina Nagaraju, Lisa G. Rider, Chenguang Fan, Yi Wen Chen, Megan Mitsak, Rashmi Rawat, Kathleen Patterson, Cecilia Grundtman, Frederick W. Miller, Paul H. Plotz, Eric Hoffman, Ingrid E. Lundberg

Research output: Contribution to journalArticlepeer-review

Abstract

Background: While vascular and immune abnormalities are common in juvenile and adult dermatomyositis (DM), the molecular changes that contribute to these abnormalities are not clear. Therefore, we investigated pathways that facilitate new blood vessel formation and dendritic cell migration in dermatomyositis. Methods: Muscle biopsies from subjects with DM (9 children and 6 adults) and non-myositis controls (6 children and 7 adults) were investigated by immunohistochemistry using antibodies that recognize existing (anti-CD146) and newly formed blood vessels (anti-αVβ3) and mature dendritic cells (anti-DC-LAMP). Blood vessel quantification was performed by digitalized image analysis. Additional muscle biopsies from subjects with adult DM and non-myositis controls were used for global gene expression profiling experiments. Results: A significant increase in neovascularization was found in muscle biopsies of DM patients; neovascularization (αVβ3 positive capillaries and vessels per muscle fiber) was much higher in juvenile than in adult DM patients (control vs juvenile DM: Mean ± SE: 0.06 ± 0.01 vs 0.6 ± 0.05; p <0.0001 and control vs adult DM: Mean ± SE: 0.60 ± 0.1 vs 0.75 ± 0.1; p = 0.051). Gene expression analysis demonstrated that genes that participate not only in angiogenesis but also in leukocyte trafficking and the complement cascade were highly up regulated in DM muscle in comparison to age matched controls. DC-LAMP positive dendritic cells were highly enriched at perivascular inflammatory sites in juvenile and adult DM patients along with molecules that facilitate dendritic cell transmigration and reverse transmigration (CD142 and CD31). Conclusion: These results suggest active neovascularization and endothelial cell activation in both juvenile and adult DM. It is likely that close association of monocytes with endothelial cells initiate rapid dendritic cell maturation and an autoimmune response in DM.

Original languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Autoimmune Diseases
Volume3
DOIs
StatePublished - Feb 20 2006
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy

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