Abstract
Mangiferin has been identified as a potent cardioprotective factor that enhances high-density lipoprotein cholesterol levels in plasma. The aim of this study was to investigate the impact of mangiferin on macrophage cholesterol efflux and the development of atherosclerosis. The results showed that mangiferin injection significantly decreased atherosclerotic plaque size, and reduced plasma levels of low-density lipoprotein cholesterol, triglyceride, and total cholesterol in apoE knockout mice, whereas reverse cholesterol transport efficiency and high-density lipoprotein cholesterol levels were enhanced. In vitro study showed that mangiferin prevented lipid accumulation and promoted [3H]-cholesterol efflux from acetylated LDL-loaded RAW264.7 macrophages with an increase in the expression of ATP binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα) and peroxisome proliferator-activated receptor-γ (PPARγ). Moreover, transfection of PPARγ siRNA or LXRα siRNA markedly abolished the positive effects of mangiferin on ABCA1/G1 expression and cholesterol efflux. The opposite effects were observed after treatment with PPARγ agonist rosiglitazone or LXRα agonist T0901317. In conclusion, mangiferin may attenuate atherogenesis by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1/G1 pathway.
Highlights
Cardiovascular disease (CVD) is one of the most common causes of morbidity and death worldwide [1]
The results showed that mangiferin injection dramatically attenuated atherosclerotic lipid accumulation (Figure 1A–1C) and lesion size (Figure 1D and 1E) and increased collagen content (Supplementary Figure 1) in aortic roots compared with those of control mice
We examined whether the peroxisome proliferator-activated receptor-γ (PPARγ)/liver X receptor-α (LXRα) pathway is implicated in the positive effects of mangiferin on ABCA1/G1 expression and cholesterol efflux
Summary
Cardiovascular disease (CVD) is one of the most common causes of morbidity and death worldwide [1]. Atherosclerosis (AS), the underlying pathophysiological basis of CVD, is classed as a disease of aging and is characterized by the deposition of foam cells within the arterial wall [2]. The initial and key step of RCT is ATP-binding cassette transporter A1/G1 (ABCA1/G1)mediated cholesterol efflux from nonhepatic peripheral tissues (e.g. macrophages and vascular smooth muscle cells) to extracellular lipid acceptors, resulting in HDL formation [5]. Suppression of ABCG1 expression by antisense oligonucleotides can decrease phospholipid and cholesterol efflux from lipid-laden macrophages to HDL [8]. Charvet et al [9] reported that ABCA1-/-/ABCG1-/mice displayed reduced cholesterol efflux from peritoneal macrophages, massive foam cell infiltration in the heart, larger proximal aortic root lesion areas and typical atherosclerotic plaques with fibrous caps compared to those of a control group. Enhancement of ABCA1 and ABCG1 expression can greatly alleviate macrophage lipid deposition and atherogenesis [10]
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