Quercetin has a protective effect on atherosclerosis via enhancement of autophagy in ApoE‑/‑ mice

Abstract

The present study examined the involvement of autophagy as a mechanism in the protective effect of quercetin (QUE) on atherosclerosis (AS) in ApoE−/− mice. An AS model was established by feeding ApoE−/− mice a high-fat diet (HFD). Mice were divided into four experimental groups: The model, QUE, 3-methyladenine (3-MA) and QUE + 3-MA groups. Additionally, age-matched wild-type C57BL/6 mice were used as a Control group. Autophagosomes in the aorta were examined using a transmission electron microscope. Aorta pathology, serum lipid accumulation and collagen deposition were determined by hematoxylin and eosin, Oil Red O and Masson staining, respectively. The levels of cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and interleukin-18 (IL-18) were measured using ELISA assays. Protein levels of mTOR, microtubule associated protein 1 light chain 3a (LC3), P53 and cyclin dependent kinase inhibitor 1A (P21) in the aorta were analyzed using western blotting. ApoE−/− mice which were fed HFD exhibited substantial AS pathology, no autophagosomes, higher levels of TNF-α, IL-1β, IL-18 and mTOR and lower ratios of LC3 II/I. All these alterations were ameliorated and aggravated by QUE and 3-MA treatment, respectively. The inhibition of AS by QUE may be associated with the enhancement of autophagy and upregulation of P21 and P53 expression.

Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment

“…Both these effects resulted in the retardation of atherosclerotic development. Antioxidant properties of quercetin in atherosclerosis is believed to be implemented through the upregulation of the autophagy in endothelial cells [90,91].…”

Therapeutic Potential of Quercetin as an Antiatherosclerotic Agent in Atherosclerotic Cardiovascular Disease: A Review

“…TNF-α, IL-1β, and IL-18 are the key inflammatory factors between autophagy and inflammation. A previous study revealed that Qu stabilizes AS plaques and inhibits AS development by reducing the production of the proinflammatory cytokines TNF-α, IL-1β, and IL-18, a mechanism which involves the induction of autophagy [83]. Weakened autophagy takes place in all major cell types in AS plaques, resulting in impaired macrophage apoptosis and increased senescence of blood vessel endothelial and smooth muscle cells.…”

“…mTOR, a key molecule in the process of autophagy induction, integrates multiple upstream signaling pathways and interacts with regulator proteins [84]. It also reported that Qu could downregulate the expression levels of mTOR, P53, and cyclin-dependent kinase inhibitor 1A (P21), enhance autophagy, and delay senescence [83]. Autophagy has also been termed as lipophagy, which involves the degradation of intracellular lipid droplets and contributes to cellular lipid metabolism [85].…”

Pathophysiology of atherosclerosis: Association of risk factors and treatment strategies using plant‐based bioactive compounds

“…Due to its anti‐inflammatory and antioxidant properties, it reduces the oxidative stress via various pathways which include NF‐κB‐dependent mechanism and/or by preventing the activation of pro‐inflammatory or oxidative stress mediators and thereby directly reducing cytokine formation (Gunawardena, Govindaraghavan, & Münch, 2014). It is also found to inhibit fat accumulation in liver of experimental mice on high‐fat diet (Cao, Jia, Shen, et al, 2019; Garelnabi, Mahini, & Wilson, 2014). Quercetin shows therapeutic potential for the prevention and treatment of many diseases such as CVDs, neurodegenerative diseases, and in many forms of cancer (Ay et al., 2016; Wang et al., 2016).…”