Icariside II prevents hypertensive heart disease by alleviating endoplasmic reticulum stress via the PERK/ATF-4/CHOP signalling pathway in spontaneously hypertensive rats

Abstract

Objectives Reducing endoplasmic reticulum stress (ERS)‐induced cardiomyocyte apoptosis is a key strategy for preventing hypertensive heart disease. In our previous study, Icariside II can improve left ventricular remodelling in spontaneously hypertensive rats (SHRs). This study aims to determine whether Icariside II can exert its effect by inhibiting ERS‐induced cardiomyocyte apoptosis via the PERK/ATF‐4/CHOP signalling pathway. Methods Spontaneously hypertensive rats were randomly divided into model group and Icariside II groups. The rats in the Icariside II groups were intragastrically administrated with Icariside II 4, 8 and 16 mg/kg from 14 to 26 week‐age, respectively. The left ventricular function was measured at the 18, 22 and 26 week‐age by small animal ultrasound. At the end of the 26th week, cardiomyocyte apoptosis was analysed and the levels of GRP78, PERK, ATF‐4 and CHOP gene and protein were detected. Key findings The function of left ventricular became declined with age in SHRs, but improved in Icariside II groups. Myocardial apoptosis was aggravated in SHRs, but alleviated in Icariside II groups. Icariside II could reduce the levels of GRP78, PERK, ATF‐4, CHOP gene and protein that increased in SHRs. Conclusions Icariside II prevents hypertensive heart disease by alleviating ERS‐induced cardiomyocyte apoptosis, and its mechanism is related to the impediment of the PERK/ATF‐4/CHOP signalling pathway.

Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix

“…Therefore, a rapid up-regulation of GRP78 is considered as the most sensitive marker of ER stress. CCAAT/enhancer binding protein homologous protein (CHOP) is an important signaling molecule for pro-apoptosis, and ER stress-specific transcription factor, which has a low expression under normal conditions but a high expression under ER stress [9]. Thus, CHOP is considered as a marker of ER stress.…”

Angelica sinensis Polysaccharide Alleviates Myocardial Fibrosis and Oxidative Stress in the Heart of Hypertensive Rats

“…It is known that the decrease in EF and FS indicates that spontaneously hypertensive rats (SHRs) exhibited ventricular remodeling and dysfunction [ 8 ]. In this study, we established an HFD-induced HHD rat model according to the previous report [ 14 ].…”

“…The left ventricle function was measured as described [ 8 ] at the end of the experiment. Briefly, the rats were fixed on an animal operation platform after anesthesia.…”

“…For example, SINI Decoction (SND) is used to prevent and treat CVDs [ 6 ]. As one of the active components of Epimedium, icariside II improved left ventricular remodeling [ 7 ] and alleviated endoplasmic reticulum stress- (ERS-) induced cardiomyocyte apoptosis in spontaneously hypertensive rats (SHRs) [ 8 ]. The Lixinshui prescription was created by chief physician Zeng Xuewen to improve the cardiac function status of patients with chronic heart failure (heart edema syndrome).…”

Recent Advances on Drug Development and Emerging Therapeutic Agents Through Targeting Cellular Homeostasis for Ageing and Cardiovascular Disease

“…The study found Icariside II alleviated hypertension-mediated cardiomyocyte apoptosis and prevented the decline in cardiac function in the rats. Icariside II reduced the expression of GRP78, CHOP, PERK, and ATF4 at both the protein and mRNA level to alleviate the extent of ER stress, reducing the percentage of apoptotic cells ( Wu et al, 2019b ). Icariside II has also been implemented in autophagy.…”