Extracellular Cyclophilin A, Especially Acetylated, Causes Pulmonary Hypertension by Stimulating Endothelial Apoptosis, Redox Stress, and Inflammation.

ABSTRACT:

Objective

Oxidative stress and inflammation play key roles in the development of pulmonary arterial hypertension (PAH). Cyclophilin A (CypA) is secreted in response to oxidative stress and promotes inflammation and cardiovascular disease. Endothelial cell (EC) dysfunction is an early event in the pathogenesis of PAH. We evaluated the role of extracellular CypA in PAH and compared the effects of acetylated CypA (AcK-CypA, increased by oxidative stress) and CypA on EC dysfunction.

Approach and results

In transgenic mice that express high levels of CypA in EC specifically, a PAH phenotype was observed at 3 months including increased right ventricular systolic pressure, α-smooth muscle actin expression in small arterioles, and CD45-positive cells in the lungs. Mechanistic analys

SUBMITTER: Xue C 

PROVIDER: S-EPMC5515294 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature