Inflammation, lipid metabolism dysfunction, and hypertension: Active research fields in atherosclerosis-related cardiovascular disease in China

Abstract

Atherosclerosis-related cardiovascular disease is one of the leading causes of death in China [1]. With advances in our understanding of the molecular mechanisms of atherosclerosis vascular inflammation, lipid metabolism dysfunction, and hypertension are regarded as the main pathogenetic pathways of both early atherogenesis and advanced plaque rupture [2,3]. Currently, much attention is being paid to the control of these pathways, which offers the potential for development of novel therapeutic approaches in the treatment of cardiovascular disease in China.In the past few decades, considerable evidence has underscored that atherosclerosis is a chronic inflammatory disease of the arterial wall, where numerous molecular inflammatory components such as organophosphate and lipopolysaccharide (LPS) play crucial roles in the development of atherosclerosis [4,5]. ATP-binding cassette transporter A1 (ABCA1), a cytomembrane transporter first cloned in 1994, has been identified as playing a key role in cholesterol reverse transport (RCT), which is regarded as anti-atherosclerotic. Evidence from many recent studies indicates that inflammation impairs RCT, and many atherogenic-related mediators play distinct regulatory roles in ABCA1 expression [2]. Liu and colleagues [6] (South Central University) investigated the effect of paraoxon, an active metabolite of organophosphorus insecticide that increases cholesterol retention in macrophages [4], on ABCA1 expression and ABCA1-dependent cholesterol efflux in RAW 264.7 macrophage-derived foam cells, and found that paraoxon significantly downregulated ABCA1 expression and reduced ABCA1-dependent cholesterol efflux through cyclic AMP signaling pathway. Our group [7,8] (University of South China) found that LPS and interferon (IFN)-γ can downregulate expression of ABCA1 and promote accumulation of lipid and decrease cellular cholesterol efflux in THP-1 macrophage-derived foam cells.Vascular endothelial dysfunction is known as the primary step in vascular inflammation and atherogenesis. Liu and colleagues [9] (Peking Union Medical College and Chinese Academy of Medical Sciences) discovered that human paraoxonase gene cluster transgenic overexpression represses atherogenesis and promotes atherosclerotic plaque stability in apoE-null mice. They also found that endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apoE-deficient mice [10]. Liu et al. [11] (Central South University) found that treatment with paraoxon resulted in significant inhibition of endothelium-dependent relaxation (EDR) in rabbits as well as a significant decrease of endothelial nitric oxide synthase (eNOS) activity in isolated aorta. These findings suggest that subchronic exposure to environmentally relevant matter such as LPS and organophosphate, even at low concentrations, potentiates inflammation, cholesterol retention, and

Apolipoprotein A-I inhibits LPS-induced atherosclerosis in ApoE−/− mice possibly via activated STAT3-mediated upregulation of tristetraprolin

“…As the major cell type for the innate immune response and cholesterol metabolism, macrophages are considered to be crucial regulatory targets to inhibit the development of atherosclerosis [36] . After activation, the infiltration of macrophages into the vessel wall is a key step in the inflammatory response contributing to the initiation of atherosclerosis [37] . Our study has demonstrated that the infiltration of CD68-positive macrophages in the atherosclerotic lesions of LPS-treated mice was clearly increased.…”

AMP-activated protein kinase activation mediates CCL3-induced cell migration and matrix metalloproteinase-2 expression in human chondrosarcoma

“…Epidemiological studies have shown that energy availability is associated with an increased risk of several metabolic diseases such as obesity, hypertension, diabetes, and induced cancers [15,16]. Aberrant energy metabolism may induce systemic and chronic inflammation both at the cellular and whole-body levels, and hence provide the microenvironment [17].…”

WGCNA-Based Identification of Hub Genes and Key Pathways Involved in Obesity

“…The main symptoms of obesity are weight gain, excessive accumulation of visceral fat, hyperlipidemia, etc [2]. In addition, obesity is a direct threat to human health and increases the risk of secondary diseases such as type 2 diabetes, nonalcoholic fatty liver, coronary atherosclerosis and tumors [3].Obesity is a chronic systemic metabolic disease in which the excess adipose tissue produced by obesity produces in ammation through the secretion of cytokines, while the neuroendocrine and metabolic energy balance systems act as a basic survival mechanism to resist the loss of stored fat. Obesity is therefore a pathological metabolic state that disrupts energy homeostasis and causes damage to other organs and systems.…”