Development of a treatment for pulmonary arterial hypertension focusing on inflammatory endothelial dysfunction
Description: In this study, we used the severe PAH model (SuHx) to test the hypothesis that the onset of PAH and right heart failure involve inflammatory endothelial dysfunction in the lung and coronary blood vessels. In SuHx rats, Endothelium-dependent vasodilator responses were significantly attenuated in the middle and small arteries in the right coronary artery of SuHx rats. Endothelin receptor antagonist treatment recovered the endothelium-dependent vasodilator responses, improved the inflammatory state of the right ventricle and restored cardiac function. We also created IL-6 knockout (KO) rats using CRISPR/Cas9 genome editing. IL-6KO rats showed significant resistance to PAH. These results suggests that endothelial dysfunction of coronary arteries is involved in the onset of right heart failure, and that inhibition of inflammatory signals may be a promising new treatment for refractory PAH.
Amount: ¥4,030,000
Funding type: fellowship
Funder scheme: Grant-in-Aid for Young Scientists (B)
Start date: 2017-04-01
End date: 2019-03-31
Investigator: Tadakatsu Inagaki
Institution: National Cardiovascular Center Research Institute
Funded outputs count: 4
Funder award ID: 17K16033
OpenAlex ID: G15701844