క్లినికల్ & ప్రయోగాత్మక కార్డియాలజీ
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నైరూప్య

Pulmonary Expression of Non-Canonical Wnt Signaling is Upregulated in Pulmonary Hypertension Secondary to Left Ventricular Dysfunction

Jao-Yu Lin1, Yi-Ching Liu2, Chee-Yin Chai3, I-Chen Chen2,4,5, Jwu-Lai Yeh5,6, Jong-Hau Hsu2,4,5, Bin-Nan Wu5,6*, Zen-Kong Dai2,4,5*

Pulmonary hypertension is a life-threatening progressive disease with few curable therapies due to its diversity and complexity. It results from increased pulmonary vascular tone and pulmonary vascular remodelling, with the aberrant Proliferation and Migration of Smooth Muscle Cells (PASMCs). The pulmonary vascular remodelling is more crucial than vasoconstriction in the development of human PH. Wnt is a family of secreted glycoproteins with varied expressions and functions. Its signalling, divided into the canonical and the non-canonical pathways, can regulate cell proliferation and cell migration pathways. Altered Wnt expressions can result in dysregulated cellular proliferation through extracellular receptors. The reactivation of fetal Wnt genes seen in embryonic development has been reported in a wide range of human pathologies, including cancers and lung disease. The exact mechanism of dysregulated Wnt expression on pulmonary vascular remodelling remains unresolved in pulmonary hypertension. We studied whether the disruption of the canonical or the non-canonical Wnt signalling played the greater roles in the development of PH by Aortic Banding for 42 days (AOB₄₂). Subsequently, pulmonary Wnt5a and Wnt11 protein levels were significantly higher in AOB₄₂ and significantly up-regulated pulmonary mRNA expressions of Wnt2 and Wnt11 were observed in AOB₄₂. In contrast, pulmonary mRNA expressions of the canonical specific Wnt3A and Wnt7A were decreased in AOB₄₂.