Valsartan Regulates PI3K/AKT Pathways through lncRNA GASL1 to Improve Isoproterenol-Induced Heart Failure.

Abstract

OBJECTIVE:

This study is aimed at determining the expression and function of the GASL1 and PI3K/AKT pathways in isoproterenol- (ISO-) induced heart failure (HF). To determine the moderating effect of valsartan (VAL) on the progression of ISO-induced HF and to elucidate the related mechanism.

MATERIALS AND METHODS:

First, in in vivo experiment, we examined the effect of VAL on cardiac function in rats with ISO-induced HF. Similarly, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the effect of VAL on ISO-treated rat primary cardiomyocytes. Then, si-GASL1-transfected primary cardiomyocytes were constructed and Ad-si-GASL1 was injected through rat tail vein to achieve the effect of lowering GASL1 expression, so as to investigate the role of GASL1 in VAL's treatment of ISO-induced HF.

RESULTS:

In ISO-induced HF rat models, the GASL1 decreased while PI3K and p-AKT expressions were abnormally elevated and cardiac function deteriorated, and VAL was able to reverse these changes. In primary cardiomyocytes, ISO induces apoptosis of cardiomyocytes, and expression of GASL1 decreased while PI3K and p-AKT were abnormally elevated, which can be reversed by VAL. The transfection of primary cardiomyocytes with si-GASL1 confirmed that GASL1 affected the expression of PI3K, p-AKT, and the apoptosis of primary cardiomyocytes. Rat myocardium injected with Ad-si-GASL1 was found to aggravate the cardiac function improved by VAL.

CONCLUSIONS:

This study was the first to confirm that VAL improves ISO-induced HF by regulating the PI3K/AKT pathway through GASL1. And this study demonstrated a significant correlation between HF, VAL, GASL1, and the PI3K/AKT pathway.

• Authors: Jian Zhou, Xiujuan Duan, Jibing Wang, Yunhong Feng, Jiangyong Yuan
• Journal: Disease markers (Dis Markers) Vol. 2022 Pg. 1447399 ( 2022) ISSN: 1875-8630 [Electronic] United States
• PMID: 35035607 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Jian Zhou et al.

Chemical References

• Carrier Proteins
• PI3KAP protein, rat
• RNA, Long Noncoding
• long non-coding RNA GASL1, human
• Valsartan
• Isoproterenol

Topics

• Animals
• Apoptosis (drug effects)
• Carrier Proteins
• Heart Failure (chemically induced, genetics)
• Humans
• Isoproterenol (pharmacology)
• Male
• Myocardium (metabolism)
• Myocytes, Cardiac (drug effects)
• RNA, Long Noncoding (blood, genetics)
• Rats
• Signal Transduction (drug effects)
• Valsartan (pharmacology)