Recent studies indicate high density lipoproteins (HDL) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma, are dysfunctional and extensively oxidized by myeloperoxidase (MPO), while in vitro oxidation of apoA1/HDL by MPO impairs its cholesterol acceptor function. We developed a high affinity monoclonal antibody (mAb) that specifically recognizes apoA1/HDL modified by the MPO/H2O2/Cl-system using phage display affinity maturation. An oxindolyl alanine (2-OH-Trp) moiety at tryptophan 72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirm a critical role for apoA1 Trp72 in MPO-mediated inhibition of ABCA1-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation, but accounts for 20% of the apoA1 in atherosclerotic plaque. OxTrp72-apoA1 recovered from human atheroma or plasma was lipid-poor, virtually devoid of cholesterol acceptor activity, and demonstrated both potent pro-inflammatory activities on endothelial cells and impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n=627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a pro-atherogenic process in the artery wall.
Observational studies have shown that low serum levels of vitamin D have been associated with an atherogenic lipid profile. However, the intervention studies gave divergent results. We conducted a meta-analysis of randomized controlled trials that evaluated the effects of vitamin D supplementation on blood lipids. A systematic literature search was conducted via MEDLINE, Cochrane library, and EMBASE for randomized controlled clinical trials assessing the effects of vitamin D supplementation on lipids. The mean change in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) from baseline was treated as a continuous variable. In all, 12 clinical trials consisting of 1346 participants were included in the analysis. The pooled estimate of effect for vitamin D supplementation on LDL-C was 3.23 mg/dl (95% confidence interval, 0.55 to 5.90 mg/dl). No statistically significant effects for vitamin D supplementation were observed for TC, HDL-C and TG (differences in means were 1.52 mg/dl (-1.42 to 4.46 mg/dl), -0.14 mg/dl (-0.99 to 0.71 mg/dl) and -1.92 mg/dl (-7.72 to 3.88 mg/dl) respectively). The lipid modulating effects of vitamin D supplementation should be further investigated though large-scale, randomized trials with adequate doses which can effectively elevated the active form of vitamin D in plasma and with proper population which has hyperlipemia as an inclusion criterion.
Cardiac involvement has been reported in patients with COVID-19, which may be reflected by electrocardiographic (ECG) changes. Two COVID-19 cases in our report exhibited different ECG manifestations as the disease caused deterioration. The first case presented temporary SIQIIITIII morphology followed by reversible nearly complete atrioventricular block, and the second demonstrated ST-segment elevation accompanied by multifocal ventricular tachycardia. The underlying mechanisms of these ECG abnormalities in the severe stage of COVID-19 may be attributed to hypoxia and inflammatory damage incurred by the virus.
Obesity, a significant risk factor for various chronic diseases, is universally related to dyslipidemia mainly represented by decreasing high-density lipoprotein cholesterol (HDL-C), which plays an indispensible role in development of cardiovascular disease (CVD). However, the mechanisms underlying obesity and low HDL-C have not been fully elucidated. Previous studies have focused on the alteration of HDL catabolism in circulation following elevated triglyceride (TG). But recent findings suggested that liver and fat tissue played pivotal role in obesity related low HDL-C. Some new molecular pathways like microRNA have also been proposed in the regulation of HDL metabolism in obesity. This article will review recent advances in understanding of the potential mechanism of low HDL-C in obesity.
Psoriasis is a chronic, systemic, hyper-proliferative immune-mediated inflammatory skin disease. The results of epidemiological investigations have shown that psoriasis affects around 2% of the general population worldwide, and the total number of psoriasis patients is more than 6 million in China. Apart from the skin manifestations, psoriasis has been verified to associate with several metabolic comorbidities, such as insulin resistance, diabetes and obesity. However, the underlying mechanism is still not elucidated. Adipocytes, considered as the active endocrine cells, are dysfunctional in obesity which displays increased synthesis and secretion of adipokines with other modified metabolic properties. Currently, growing evidence has pointed to the central role of adipokines in adipose tissue and the immune system, providing new insights into the effect of adipokines in linking the pathophysiology of obesity and psoriasis. In this review, we summarize the current understanding of the pathological role of adipokines and the potential mechanisms whereby different adipokines link obesity and psoriasis. Furthermore, we also provide evidence which identifies a potential therapeutic target aiming at adipokines for the management of these two diseases.
Long-term controversy regarding the role of angiopoietin-like protein 8 (ANGPTL8) in beta-cell proliferation and diabetes progression made it a research spotlight. Recently, the controversy was resolved. Although ANGPTL8 could not control beta-cell expansion and islet function, ANGPTL8 was still considered as a novel but atypical member in the ANGPTL family because of its unique structure and crucial effects on lipid metabolism. Besides, ANGPTL8 also participated in some other disorders such as non-alcoholic fatty liver disease and renal dysfunction. Understanding the features of ANGPTL8 may offer new diagnostic and therapeutic approaches to metabolic-related diseases. Therefore, we reviewed most recent findings about ANGPTL8 and aimed to provide an integrated picture of ANGPTL8.
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