Modification of hyaluronan by heavy chains of inter-alpha-inhibitor in idiopathic pulmonary arterial hypertension [Glycobiology and Extracellular Matrices]

January 8th, 2014 by Lauer, M. E., Aytekin, M., Comhair, S. A., Loftis, J., Tian, L., Farver, C. F., Hascall, V. C., Dweik, R. A.

We previously reported an altered hyaluronan (HA) metabolism in idiopathic pulmonary arterial hypertension (IPAH) lung tissue and cultured smooth muscle cells. Hyaluronan was present in the smooth muscle cell layer surrounding the pulmonary vasculature and in plexigenic lesions. Additionally, cultured pulmonary artery smooth muscle cells (PASMCs) produced spontaneous HA cable structures, without additional stimuli, that were leukocyte adhesive. We now present evidence that the hyaluronan that accumulates in IPAH plexigenic lesions is a pathological form of HA in which heavy chains (HCs) from the serum-derived proteoglycan inter-alpha-inhibitor (IαI) are covalently attached to the HA backbone to form a pathological HC-HA complex. CD45 positive leukocytes were identified within these HC-HA matrices. Elevated mRNA levels of the enzyme that transfers HCs to HA, known as tumor-necrosis-factor-stimulated-gene-6 (TSG-6), were detected in IPAH lung tissue.
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