Angiogenesis and Roles of Adhesion Molecules in Psoriatic Disease

Angiogenesis, the process of new vessel formation from preexisting vessels, involves complex interactions between multiple cell types and molecular players. It is central to the pathology of psoriatic diseases. Angiogenesis in psoriatic skin happens mainly through tortuous elongation without new branching, unlike sprouting (branching) angiogenesis seen in tumors. From the venular end of intrapapillary dermal capillary loops, long new stretches of fenestrated dilated venular capillaries are added during plaque formation. These venules are sticky due to upregulation of adhesion molecules. Whether the initial trigger of psoriasis is epithelium under stress or inflammatory cells recruited by psoriatic venules has been a drifting paradigm. A combination of pro-angiogenic factors—small vascular endothelial growth factor (VEGF) isoforms, angiopoietin 2, interleukin (IL) 17, antimicrobial alarmins, and so forth—are secreted with DNA, in the neutrophil extracellular trap (NET) in the epidermis and in the mast cell extracellular trap (MCET) in the dermis, in psoriatic lesions. Neutrophil subtypes and bone marrow–derived cells (BMDCs) play newly discovered roles in angiogenesis. Angiogenesis has been extensively studied in rheumatoid arthritis (RA), but not much in psoriatic arthritis (PsA), as it was considered to be similar to RA. However, despite being inflammatory arthritis, the nature of the pathology in PsA is different from that in RA, and some PsA may even overlap with osteoarthritis (OA). The angiogenesis in RA involves mostly sprouting angiogenesis with straight branching vessels visible in arthroscopy, whereas PsA involves rapid dramatic growth of bushy tortuous nonbranching vessels visible in arthroscopy. Spatial and temporal organization of VEGF, adhesion molecules, angiopoietin 2, transforming growth factor (TGF) β, and so forth, is different, and IL17 plays a more central role than tumor necrosis factor (TNF) α. Attempts to control angiogenesis through blocking of adhesion and signaling are still in their infancy. Blocking of isolated steps of angiogenesis has issues, for example, paradoxical worsening and immunosuppression. Efalizumab, an inhibitor of αLβ2 integrin, was approved by the Food and Drug Administration in 2003 but was retracted in 2009 due to cases of fatal progressive multifocal leukoencephalopathy (PML), which was a major setback.