Augmentation of autophagy by atorvastatin via Akt/mTOR pathway in spontaneously hypertensive rats

Abstract

Autophagy is activated in hypertension-induced cardiac hypertrophy. However, the mechanisms and significance of an activated autophagy are not clear. This study was designed to determine the role of atorvastatin (ATO) in cardiac autophagy and associated benefits on cardiac remodeling and left ventricular function in spontaneously hypertensive rats (SHRs). Twenty-eight male SHRs at 8 weeks of age were randomized to treatment with vehicle (saline solution; SHR+V) or ATO (SHR+ATO; 50 mg kg(-1) per day) for 6 or 12 months. Age-matched male Wistar-Kyoto (WKY) rats were used as normotensive controls. Cardiac magnetic resonance was used to evaluate cardiac function and structure. Compared with WKY rats, SHRs showed significant left ventricle (LV) dysfunction, remodeling and increases in cardiomyocyte size, which were all attenuated by 6 and 12 months of ATO treatment. Compared with WKY rats, autophagy was activated in the hearts of SHRs and this effect was amplified by chronic ATO treatment, particularly following 12 months of treatment. Protein expression levels of microtubule-associated protein-1 light chain 3-II and beclin-1, the biomarkers of an activated cardiac autophagy, were significantly elevated in ATO-treated versus vehicle-treated SHRs and control WKY rats. Cardiac Akt and phosphorylated mammalian target of rapamycin (mTOR) expression were also increased in the hearts of SHR versus WKY rats, and this effect was attenuated by ATO treatment. These findings suggest that ATO-mediated improvements in LV function and structure in SHRs may be, in part, through its regulation of cardiac autophagy via the Akt/mTOR pathway.

The Different Effects of Atorvastatin and Pravastatin on Cell Death and PARP Activity in Pancreatic NIT-1 Cells

“…Our study results showed that atorvastatin treatment markedly reduced cell viability compared to untreated NIT-1 cells through increasing PARP1 activation and subsequently inducing necrosis and autophagy induction. This finding confirms previous findings that atorvastatin induced autophagic activity in vivo and in vitro [37–40]. In 2012, Lim et al demonstrated that pravastatin can improve renal function in CsA-induced autophagic cell death through reducing LC3-II and P62 expression.…”

Altered mTOR and Beclin-1 mediated autophagic activation during right ventricular remodeling in monocrotaline-induced pulmonary hypertension

“…Thus, LC3 and the ratio of LC3-II/LC3-I are considered markers of autophagy. Autophagosomes can be observed using a transmission electron microscope and are considered “gold standards” in terms of morphological/ultrastructural evidence of autophagy activation, [13] while upregulation of p62 poses as a marker of autophagosomal clearance [14, 15]. …”

The Role of Probiotics in Lipopolysaccharide-Induced Autophagy in Intestinal Epithelial Cells

“…When cells are exposed to certain internal and external environment stimuli such as nutritional stress or invasion by microbial or viral pathogens, increased autophagy is induced to maintain cell survival [1,3]. Autophagy also plays a crucial mediating role in the development of various pathologies in humans, including neurodegeneration [4], tumor formation [5,6], and cardiovascular disease [7].…”