Stanozolol promotes lipid deposition in the aorta through an imbalance in inflammatory cytokines and oxidative status in LDLr knockout mice fed a normal diet

Abstract

The aim of the study was to evaluate the effect of an anabolic steroid, stanozolol, in a model of atherosclerosis and to investigate the involvement of the modulation of the inflammatory cytokines and oxidative stress in vascular lipid deposition.Low-density lipid receptor-deficient (LDLr−/−) mice were fed a standard chow diet and were each week injected subcutaneously either saline (control C group) or 20 mg/kg stanozolol (S group). After 8 weeks, the levels of cholesterol, oxidized LDL (OxLDL) and cytokines were measured in plasma, lipid deposition in aorta was evaluated by en face analysis, and thiobarbituric acid-reactive substances and oxidation protein were determined in liver. The S group demonstrated increases in vascular lipid deposition, triglycerides and non-HDL cholesterol levels. Stanozolol increased tumour necrosis factor alpha (TNF-α) and decreased interleukin-10 as well as increased the TNF-α/IL-10 ratio. Furthermore, oxidative stress was observed in the S group, as indicated by an increase in the plasma OxLDL, as well as by lipid peroxidation and oxidation of proteins in the liver. Chronic treatment with stanozolol promoted lipid deposition in the LDLr −/− mice that could be attributed to a modification of the circulating cytokine levels and systemic oxidative stress. Our results suggest that the anabolic steroid stanozolol in the absence of functional LDL receptors by increasing systemic inflammation and oxidative stress may increase the risk of development and progression of atherosclerosis.

Bisphenol S Induces Ectopic Angiogenesis in Embryos via VEGFR2 Signaling, Leading to Lipid Deposition in Blood Vessels of Larval Zebrafish

“…Epidemiological studies of exogenous pollutants usually discover a potential risk of AS by detecting remarkable endpoints, such as carotid intimal thickness, , the degree of coronary arteriostenosis, and the ankle-brachial index . Subsequently, although many fundamental and innovative studies have attempted to explore the atherogenic mechanism using apoE –/– and/or ldlr –/– hyperlipidemia mammals prone to produce plaques following a normal or high-fat diet, − ,, it is still difficult to link vascular lesions to lipid deposition in budding AS in vivo. Indeed, blood vessels at bends, bifurcations, and stenoses are susceptible to lipid deposition because of decreased blood flow velocity. − An in vitro study showed that BPA could increase the number of tubes and branch points of human endometrial endothelial cells (ECs) .…”

Reduced Levels of Testosterone Induce LDL Oxidation and Atherosclerotic Lesions Involving Inflammatory Imbalance and Reduced Macrophage Apoptosis

“…Among the in vivo experimental models that are used to study atherosclerosis, LDL receptor knockout (LDLr-/-) mice are widely used. This is due to the fact that these animals present metabolic changes and spontaneous lipid deposition in the aorta induced by aging or through interventions that characterize risk factors, such as the use of atherogenic diet (Hatch et al, 2012), castration (orchiectomy and ovariectomy) (de Oliveira et al, 2013;Hopmans et al, 2014) or treatment with supraphysiological doses of androgenic anabolic steroids (de Andrade et al, 2018). Moreover, the LDLr-/-are chosen for this study because mice present a lipoprotein profile similar to hyperlipidemic humans, since the cholesterol concentrates on the LDL fraction (Zadelaar et al, 2007).…”