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Updated: Jun 23, 2025

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Published on: May 11, 2015
NOTCH3 and Pulmonary Arterial Hypertension
Nolan M Winicki1, Cristian Puerta1, Casandra E Besse1
1Division of Cardiothoracic Surgery, University of California, 9300 Campus Point Drive, La Jolla, San Diego, CA 92037-7892, USA.
Abstract:
NOTCH3 receptor signaling has been linked to the regulation of smooth muscle cell proliferation and the maintenance of smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (World Health Organization Group 1 idiopathic disease: PAH) is a fatal disease characterized clinically by elevated pulmonary vascular resistance caused by extensive vascular smooth muscle cell proliferation, perivascular inflammation, and asymmetric neointimal hyperplasia in precapillary pulmonary arteries. In this review, a detailed overview of the specific role of NOTCH3 signaling in PAH, including its mechanisms of activation by a select ligand, downstream signaling effectors, and physiologic effects within the pulmonary vascular tree, is provided. Animal models showing the importance of the NOTCH3 pathway in clinical PAH will be discussed. New drugs and biologics that inhibit NOTCH3 signaling and reverse this deadly disease are highlighted.
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