Notch3 signalling and vascular remodelling in pulmonary arterial hypertension

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Abstract

Notch signalling is critically involved in vascular morphogenesis and function. Four Notch isoforms (Notch1-4) regulating diverse cellular processes have been identified. Of these, Notch3 is expressed almost exclusively in vascular smooth muscle cells (VSMCs), where it is critically involved in vascular development and differentiation. Under pathological conditions, Notch3 regulates VSMC switching between the contractile and synthetic phenotypes. Abnormal Notch3 signalling plays an important role in vascular remodelling, a hallmark of several cardiovascular diseases, including pulmonary arterial hypertension (PAH). Because of the importance of Notch3 in VSMC (de)differentiation, Notch3 has been implicated in the pathophysiology of pulmonary vascular remodelling in PAH. Here we review the current literature on the role of Notch in VSMC function with a focus on Notch3 signalling in pulmonary artery VSMCs, and discuss potential implications in pulmonary artery remodelling in PAH.

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Morris, H. E., Neves, K. B., Montezano, A. C., MacLean, M. R., & Touyz, R. M. (2019). Notch3 signalling and vascular remodelling in pulmonary arterial hypertension. Clinical Science. Portland Press Ltd. https://doi.org/10.1042/CS20190835

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