Atherosclerosis is an autoimmune disease caused by self- and non-self-antigens contributing to excessive activation of T and B cell immune responses. These responses further aggravate vascular infiammation and promote progression of atherosclerosis and vulnerability to plaques via releasing pro-infiammatory cytokines. Regulatory T cells (Tregs) as the major immunoregulatory cells, in particular, induce and maintain immune homeostasis and tolerance by suppressing the immune responses of various cells such as T and B cells, natural killer (NK) cells, monocytes, and dendritic cells (DCs), as well as by secreting inhibitory cytokines interleukin (IL)-10, IL-35 and transcription growth factor β (TGF-β) in both physiological and pathological states. Numerous evidence demonstrates that reduced numbers and dysfunction of Treg may be involveved in atherosclerosis pathogenesis. Increasing or restoring the numbers and improving the immunosuppressive capacity of Tregs may serve as a fundamental immunotherapy to treat atherosclerotic cardiovascular diseases. In this article, we briefiy present current knowledge of Treg subsets, summarize the relationship between Tregs and atherosclerosis development, and discuss the possibilities of regulating Tregs for prevention of atherosclerosis pathogenesis and enhancement of plaque stability. Although the exact molecular mechanisms of Treg-mediated protection against atherosclerosis remain to be elucidated, the strategies for targeting the regulation of Tregs may provide specific and significant approaches for the prevention and treatment of atherosclerotic cardiovascular diseases.

Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.

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Advanced oxidation protein products (AOPPs) are novel biomarkers of oxidative damage to proteins and a novel class of inflammatory mediators. AOPPs can promote oxidative stress (OS) and inflammation and thus participate in many pathophysiological disease processes. Atherosclerosis is a chronic inflammatory disease of blood vessels that is characterized by low-density lipoprotein infiltration into the endothelial intima and the formation of atherosclerotic plaques. Inflammation and OS are established risk factors for the formation of atherosclerosis. Accumulated studies show that AOPPs can accelerate the progression of atherosclerosis through OS and inflammation. Additionally, AOPPs can accelerate the formation of atherosclerotic plaques by inhibiting high-density lipoprotein receptor scavenger receptor class B type I-mediated high-density lipoprotein cholesterol reverse transport, leading to metabolic disturbances. Some studies have suggested that plasma AOPPs levels are independently positively correlated with blood pressure and are also independent risk factors for cardiovascular disease. AOPPs can trigger oxidative bursts of neutrophils, monocytes and phagocytic cells, increase the generation of reactive oxygen species and promote the secretion of cytokines to accelerate endothelial cell injury. Detecting the levels and inhibiting the formation of AOPPs may provide a novel approach to monitor the progress and improve the prognosis of atherosclerosis.

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Background: Tanshinone IIA (Tan IIA) and Omentin-1 have a protective role in the cardiovascular system. However, if and how Tan IIA and Omentin-1 regulate cholesterol metabolism in macrophages has not been fully elucidated. Objective: To investigate the possible mechanisms of Tan IIA and Omentin-1 on preventing macrophage cholesterol accumulation and atherosclerosis development. Methods: The effect of Tan IIA on the protein and mRNA levels of Omentin-1 and ATP-binding cassette transporter A1 (ABCA1) in macrophages was examined by Western blot and qRT-PCR assay, respectively. Cholesterol efflux was assessed by liquid scintillation counting (LSC). Cellular lipid droplet was measured by Oil Red O staining, and intracellular lipid content was detected by high performance liquid chromatography (HPLC). In addition, the serum lipid profile of apoE−/− mice was measured by enzymatic method. The size of atherosclerotic lesion areas and content of lipids and collagen in the aortic of apoE−/− mice were examined by Sudan IV, Oil-red O, and Masson staining, respectively. Results: Tan IIA up-regulated expression of Omentin-1 and ABCA1 in THP-1 macrophages, promoting ABCA1-mediated cholesterol efflux and consequently decreasing cellular lipid content. Consistently, Tan IIA increased reverse cholesterol transport in apoE−/− mice. Plasma levels of high-density lipoprotein cholesterol (HDL-C), ABCA1 expression and atherosclerotic plaque collagen content were increased while plasma levels of low-density lipoprotein cholesterol (LDL-C) and atherosclerotic plaque sizes were reduced in Tan IIA-treated apoE−/− mice. These beneficial effects were, however, essentially blocked by knockdown of Omentin-1. Conclusion: Our results revealed that Tan IIA promotes cholesterol efflux and ameliorates lipid accumulation in macrophages most likely via the Omentin-1/ABCA1 pathway, reducing the development of aortic atherosclerosis.

to be the key to maintaining the balance of cholesterol metabolism and effectively preventing the development of atherosclerosis. 2,3 MK, a potent growth factor, mainly regulates the survival of neurons in the mid-gestation period of embryogenesis. However, the expression of MK is strictly limited in adults. MK expression is increased under acute or chronic pathological conditions, such as chronic heart failure and cardiac ischemia/reperfusion injury. 4 Previous studies have found that MK affects the development of inflammatory diseases, A therosclerosis is the main pathological feature of cardiovascular and cerebrovascular diseases. As such, it has become one of the major diseases leading to increased mortality worldwide. 1 Emerging evidence suggests that dyslipidemia is a common metabolic abnormality in atherosclerosis. Importantly, macrophage phagocytosis of excess atherosclerotic lipids, differentiation into foam cells and aggregation in the arterial intima are key steps in the development of atherosclerosis. Notably, the promotion of macrophage cholesterol efflux is considered