Vasculitis

These observations raise important questions about a fascinating animal model of aortitis initially studied more than 10 years ago.^12,13 A usually nonpathogenic herpes virus (γHV68) was provided as a standard inoculum to immunologically intact mice, as well as IFNγ- and IFNγ−receptor(R)-deficient mice. While the intact mice did not develop illness, the IFNγ- and IFNγ−R-deficient mice died from aortic rupture or dissection at approximately eight to 10 weeks. When animals were serially sacrificed and studied from one to six weeks postinoculation, it was apparent that widespread viremia had occurred but that virus could be effectively cleared from the IFNγ- and IFNγ–R-deficient mice from all organs except the aortic root. Thus, despite their lack of either IFNγ- or IFNγ−R, the gene-deficient animals possessed adequate immunological redundancy in other organs and within the distal thoracic and abdominal aorta to clear virus. However, the aortic root was uniquely vulnerable.

Figure 2B: Fenestrated EC arrangements are found in capillaries that allow rapid passage of large molecules such as in endocrine and exocrine glands, gastrointestinal mucosa, and intestinal villi. In the kidney, the renal glomeruli in which pericytes are mesangial cells, a fenestrated arrangement is present; however, this is not the case within the renal vasa recta where a continuous EC microanatomy is maintained.

Conclusions

Vessels are not merely anatomic conduits that carry blood, gases, nutrients, and waste products. Furthermore, they cannot be considered in simplistic terms based only on vessel size. It is clear that vessels, even of the same caliber from different organs, have important differences in their microanatomy, chemistry, and function. They work as partners in tissue development and have unique barrier and immunologic roles in different sites. Vessels, like all other tissues, also undergo changes in time. They can be sites of topographically selective chemical and other forms of injury or can selectively harbor infectious agents. The injury–repair process that is part of adapting to life’s challenges modifies substrate and is susceptible to errors in response and repair that may include mutations. Although this process plays an important role in the pathogenesis of cancer, it has not been examined within affected vessels in vasculitis. Might mutations provide neo-antigens as one means of stimulating an immune response against vessels, and could this response even be a functionally “normal” attempt to clear a “foreign” protein?

These questions do not diminish the importance of gender effects, immunological senescence, or inheritance in establishing disease predisposition. They do, however, emphasize that vessels are site-variable, complex, specialized organs, with qualities that are probably important in determining disease patterns. We can ill afford to ignore the unique properties of vascular territories and how they change over time if we wish to better understand the pathogenesis of the vasculitides. We should begin to apply lessons from embryology and vascular biology and reach beyond the simplistic notion of vasculitis being “understood” based principally on vessel size.