Abstract
Atherosclerosis is the main cause of mortality in metabolic-related diseases, including cardiovascular disease and type 2 diabetes (T2DM). Atherosclerosis is characterized by lipid accumulation and increased inflammatory cytokines in the vascular wall, endothelial cell and vascular smooth muscle cell dysfunction and foam cell formation initiated by monocytes/macrophages. The characteristics of metabolic syndrome (MetS), including obesity, glucose intolerance, dyslipidemia and hypertension, may activate multiple mechanisms, such as insulin resistance, oxidative stress and inflammatory pathways, thereby contributing to increased risks of developing atherosclerosis and T2DM. Autophagy is a lysosomal degradation process that plays an important role in maintaining cellular metabolic homeostasis. Increasing evidence indicates that impaired autophagy induced by MetS is related to oxidative stress, inflammation, and foam cell formation, further promoting atherosclerosis. Basal and mild adaptive autophagy protect against the progression of atherosclerotic plaques, while excessive autophagy activation leads to cell death, plaque instability or even plaque rupture. Therefore, autophagic homeostasis is essential for the development and outcome of atherosclerosis. Here, we discuss the potential role of autophagy and metabolic syndrome in the pathophysiologic mechanisms of atherosclerosis and potential therapeutic drugs that target these molecular mechanisms.
Highlights
Atherosclerosis is the main cause of mortality and morbidity in metabolic-related diseases, including cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) (Weber and Noels, 2011; Barquera et al, 2015; Schneider et al, 2016)
Another study demonstrated that macrophage autophagy could be induced by Akt inhibitors, mammalian target of rapamycin (mTOR) inhibitors and mTOR-siRNA, while phosphatidylinositol 3-kinase (PI3K) inhibitors had the opposite effect, which indicates that activating autophagy of macrophage via the inhibition of the PI3K/Akt/mTOR pathway can stabilize vulnerable atherosclerotic plaques (Zhai et al, 2014)
Based on the effects of metabolic syndrome (MetS) characteristics and autophagy on the pathogenesis of atherosclerosis, we suggest that targeted autophagy therapy may be an effective and promising strategy for atherosclerosis treatment
Summary
Atherosclerosis is the main cause of mortality and morbidity in metabolic-related diseases, including cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM) (Weber and Noels, 2011; Barquera et al, 2015; Schneider et al, 2016). The details and criteria of the definition differ among different associations, such as the World Health Organization (WHO) (Alberti and Zimmet, 1998), the European Group for the Study of Insulin Resistance (EGIR) (Balkau and Charles, 1999), the National Cholesterol Education Program’s Adult Treatment Panel III (NCEP: ATP III) (Expert Panel on Detection et al, 2001) and the International Diabetes Federation (IDF) (Alberti et al, 2006), the essential characteristics include obesity, glucose intolerance, dyslipidemia and hypertension (Eckel et al, 2005; McCracken et al, 2018) (Table 1) These characteristics of MetS may contribute to insulin resistance, oxidative stress, inflammation and endothelial dysfunction, which are pivotal mechanisms associated with the pathogenesis of atherosclerosis. We discuss the role of autophagy and MetS characteristics in the pathogenesis of atherosclerosis and potential therapeutic drugs that target these molecular mechanisms
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