Pulmonary hypertension (PH) is a life-threatening disease characterized by massive remodeling of the pulmonary vessels from delicate-walled capillaries to thick-walled narrow vessels. This massively restricts gas exchange and places a strain on the right heart. Despite much progress - including by DZL scientists and clinicians - PH is still not curable.
Two experimental models have demonstrated that administration of juglone (a dye derived from walnut) reduces pulmonary vascular resistance, improves right ventricular function, and reduces vascular remodeling. The mechanism of action was identified as an enzyme (peptidylprolyl cis/trans isomerase, NIMA interacting 1) Pin 1, which acts as a molecular "switch" in cells. This protein is also increased in expression in tissue samples from patients with pulmonary arterial hypertension. Targeted inhibition of Pin 1, e.g. using juglone, appears to represent an attractive new therapeutic strategy for the treatment of PH.
Original publication: Rai N, Sydykov A, Kojonazarov B, Wilhelm J, Manaud G, Veeroju S, Ruppert C, Perros F, Ghofrani HA, Weissmann N, Seeger W, Schermuly RT, Novoyatleva T: Targeting peptidyl-prolyl isomerase 1 in experimental pulmonary arterial hypertension.
Eur Respir J. 2022 Jan 20:2101698. doi: 10.1183/13993003.01698-2021. online ahead of print. PMID: 35058248