Tipifarnib prevents development of hypoxia-induced pulmonary hypertension.

ABSTRACT:

Aims

RhoB plays a key role in the pathogenesis of hypoxia-induced pulmonary hypertension. Farnesylated RhoB promotes growth responses in cancer cells and we investigated whether inhibition of protein farnesylation will have a protective effect.

Methods and results

The analysis of lung tissues from rodent models and pulmonary hypertensive patients showed increased levels of protein farnesylation. Oral farnesyltransferase inhibitor tipifarnib prevented development of hypoxia-induced pulmonary hypertension in mice. Tipifarnib reduced hypoxia-induced vascular cell proliferation, increased endothelium-dependent vasodilatation and reduced vasoconstriction of intrapulmonary arteries without affecting cell viability. Protective effects of tipifarnib were associated with inhibition o

SUBMITTER: Duluc L 

PROVIDER: S-EPMC5408956 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature