Background: Idiopathic pulmonary arterial hypertension (IPAH) is a rare, fatal disease of unknown pathogenesis.\nEvidence from our recent study suggests that IPAH pathogenesis is related to upregulation of the Wnt/planar cell\npolarity (Wnt/PCP) pathway. We used microscopic observation and immunohistochemical techniques to identify\nexpression patterns of cascading proteinsââ?¬â?namely Wnt-11, dishevelled-2 (Dvl-2), and dishevelled-associated\nactivator of morphogenesis 1 (Daam-1)ââ?¬â?in pulmonary arteries.\nMethods: We analyzed sections of formalin-fixed and paraffin-embedded autopsied lung tissues obtained from 9\nIPAH cases, 7 associated pulmonary arterial hypertension cases, and 16 age-matched controls without pulmonary\narterial abnormalities. Results of microscopic observation were analyzed in relation to the cellular components and\nsize of pulmonary arteries.\nResults: Varying rates of positive reactivity to Dvl-2 and Daam-1 were confirmed in all cellular components\nof pulmonary arteries, namely, endothelial cells, myofibroblasts, and medial smooth muscle cells. In contrast,\nnone of these components was reactive to Wnt-11. No specific expression patterns were observed for endothelial\ncells or myofibroblasts under any experimental conditions. However, marked expression of Dvl-2 and Daam-1 was\nconfirmed in smooth muscle cells. In addition, Dvl-2 was depleted while Daam-1 expression was elevated in IPAH, in\ncontrast with specimens from associated pulmonary arterial hypertension cases and controls.\nConclusions: High Daam-1 expression may upregulate the Wnt/PCP pathway and cause IPAH.
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