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  • Review Article
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Vasculitis: determinants of disease patterns

Nature Reviews Rheumatology volume 10, pages 454–462 (2014)Cite this article

Subjects

Key Points

  • Vessels are more than merely conduits for blood, nutrients, gas exchange and waste disposal

  • The dialogue between developing and mature vessels and their resident tissues determines organ form, function, specialization, vulnerability and capacity for repair

  • Vessels of the same size in different organs are not the same, reflecting specialized functions

  • Vessels are immunologically competent structures

  • As with other tissues, growth, development and ageing of vessels are associated with adaptations (and maladaptations) that modify their function and vulnerabilities

  • The unique features that define vascular diversity provide extraordinary opportunities to explore mechanisms responsible for unique disease patterns in different forms of vasculitis

Abstract

The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. As clinicians, we distinguish one form of vasculitis from another on the basis of observed patterns of organ injury, the size of the vessels affected and histopathological findings. The terms 'small-vessel', 'medium-vessel' and 'large-vessel' vasculitis are useful clinical descriptors, but fail to inform us about why vessels of a certain calibre are favoured by one disease and not another. Classification based on vessel size also fails to consider that vessels of a specific calibre are not equally prone to injury. Distinct vulnerabilities undoubtedly relate to the fact that same-size vessels in different tissues may not be identical conduits. In fact, vessels become specialized, from the earliest stages of embryonic development, to suit the needs of different anatomical locations. Vessels of the same calibre in different locations and organs are as different as the organ parenchymal cells through which they travel. The dialogue between developing vessels and the tissues they perfuse is designed to meet special local needs. Added to the story of vascular diversity and vulnerability are changes that occur during growth, development and ageing. An improved understanding of the unique territorial vulnerabilities of vessels could form the basis of new hypotheses for the aetiopathogenesis of the vasculitides. This Review considers how certain antigens, including infectious agents, might become disease-relevant and how vascular diversity could influence disease phenotypes and the spectrum of vascular inflammatory diseases.

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Figure 1: Endothelial microvascular relationships in different organs.
Figure 2: Blood–brain barrier.
Figure 3: The renal microvascular structure and function varies with intrarenal location.
Figure 4: Developmental fate map for VSMCs.
Figure 5: Vessel-specific TLR gene expression profiles in human medium and large vessels.
Figure 6: Mice lacking IFN-γ or the IFN-γR inoculated with murine herpesvirus develop aortic root/arch site-specific aortitis.
Figure 7: HCV infection targeting the BBB.
Figure 8: Anti-GBM disease (Goodpasture syndrome) involves modification of native antigen.

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Acknowledgements

G.S.H. has received partial research support from the Harold C. Schott Foundation and the Konigsberg Family Fund for Vasculitis Research. L.H.C. is in part supported by the R. J. Fasenmyer Foundation.

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Authors and Affiliations

  1. Department of Rheumatic and Immunologic Diseases, A50, 9500 Euclid Avenue

    Gary S. Hoffman & Leonard H. Calabrese

  2. Lerner College of Medicine, Cleveland Clinic, Cleveland, 44195, OH, USA

    Gary S. Hoffman & Leonard H. Calabrese

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G.S.H. conceived the article's content, researched data for the article, wrote the first draft and reviewed/edited the manuscript before submission. L.H.C. researched data for and wrote the section on viral-associated vasculitis.

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Correspondence to Gary S. Hoffman.

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Hoffman, G., Calabrese, L. Vasculitis: determinants of disease patterns. Nat Rev Rheumatol 10, 454–462 (2014). https://doi.org/10.1038/nrrheum.2014.89

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