Αναζήτηση αυτού του ιστολογίου

Κυριακή 12 Σεπτεμβρίου 2021

Angiotensin-converting enzyme 2 alleviates pulmonary artery hypertension through inhibition of focal adhesion kinase expression

xlomafota13 shared this article with you from Inoreader

Exp Ther Med. 2021 Oct;22(4):1165. doi: 10.3892/etm.2021.10599. Epub 2021 Aug 12.

ABSTRACT

Focal adhesion kinase (FAK) is an important therapeutic target in pulmonary artery hypertension (PAH); however, the mechanism of its activation remains unknown. The present study aimed to investigate whether angiotensin-converting enzyme 2 (ACE2) could regulate FAK and alleviate PAH in a rat model of PAH established with a single administration of monocrotaline followed by continuous hypoxia treatment. In the current study, right ventricular pressure, body weight and the right ventricular hypertrophy index were measured, and hematoxylin-eosin staining was performed on lung tissues to determine whether the modeling was successful. Changes in the serum levels of FAK were measured using an ELISA kit to evaluate the association between ACE2 and FAK. The mRNA expression levels of ACE2, FAK, caspase-3 and survivin were determined using reverse transcri ption-quantitative PCR (RT-qPCR). The protein expression levels of ACE2, phosphorylated FAK/FAK, cleaved caspase-3/pro-caspase-3 and survivin were determined via western blotting. Immunohistochemistry was applied to detect the expression of FAK around the pulmonary arterioles. Apoptosis of smooth muscle cells around pulmonary arterioles was observed by TUNEL staining. After treatment with the ACE2 activator DIZE or inhibitor DX-600, the results demonstrated that ACE2 reduced PAH-induced changes in arteriole morphology compared with the control. It also inhibited FAK expression in serum. WB and RT-qPCR results suggested that ACE2 inhibited the expression of FAK and pathway-related proteins, and promoted caspase-3 expression. Additionally, ACE2 reduced FAK expression around the pulmonary arterioles and promoted smooth muscle cell apoptosis. The results indicated that ACE2 activation inhibited FAK expression, leading to alleviation of the symptoms of PAH.

PMID:34504610 | PMC:PMC8393266 | DOI:10.3892/etm.2021.10599

View on the web

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου

Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.