Journal of internal medicine
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Multicenter Study
Subclinical atherosclerosis and its progression are modulated by PLIN2 through a feed-forward loop between LXR and autophagy.
Hyperlipidaemia is a major risk factor for cardiovascular disease, and atherosclerosis is the underlying cause of both myocardial infarction and stroke. We have previously shown that the Pro251 variant of perilipin-2 reduces plasma triglycerides and may therefore be beneficial to reduce atherosclerosis development. ⋯ For the first time, we show that perilipin-2 affects susceptibility to human atherosclerosis through activation of autophagy and stimulation of cholesterol efflux. We demonstrate that perilipin-2 modulates levels of the LXR ligand 27OH-cholesterol and initiates a feed-forward loop where LXR and autophagy reciprocally activate each other; the mechanism by which perilipin-2 exerts its beneficial effects on subclinical atherosclerosis.
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The aetiology of the autoimmune disease rheumatoid arthritis (RA) involves a complex interplay between genetic and environmental factors that initiate many years before the onset of clinical symptoms. These interactions likely include both protective and susceptibility factors which together determine the risk of developing RA. More than 100 susceptibility loci have been linked to RA. ⋯ Interestingly, patients with RA develop autoantibodies many years before the clinical onset of disease, providing strong evidence that the lack of tolerance to arthritogenic antigens is amongst the earliest events in the initiation of seropositive RA. Here, we will discuss the clinical and mechanistic evidence surrounding the role of different environmental and genetic factors in the phases leading to the production of autoantibodies and the initiation of symptomatic RA. Understanding this complexity is critical in order to develop tools to identify drivers of disease initiation and propagation and to develop preventive therapeutics.
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Comparative Study
Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials.
It is questionable as to whether total serum 25 hydroxyvitamin D (T25D) levels are lower in African Americans. We measured serum T25D, free 25hydroxyvitamin D (F25D) and serum parathyroid hormone (PTH) in African American and Caucasian women and studied the effect of vitamin D dosing to determine if differences by race or age occur. ⋯ Serum F25D and T25D are lower in younger African American women, and since dietary vitamin D is similar in the groups, it is likely that the cause of low serum 25OHD in African American women is due to reduced UV exposure and reduced skin production of vitamin D.
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Obstructive sleep apnoea (OSA) and hyperlipidaemia are independent risk factors for cardiovascular disease. This study investigates the association between OSA and prevalence of hyperlipidaemia in patients of the European Sleep Apnea Database (ESADA) cohort. ⋯ Obstructive sleep apnoea, in particular intermittent hypoxia, was independently associated with the prevalence of hyperlipidaemia diagnosis.
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Observational Study
Conservative management in hypertriglyceridemia-associated pancreatitis.
Severe hypertriglyceridemia (serum triglyceride >10 mmol L-1 ) is implicated in ~9% of acute pancreatitis cases. Certain guidelines list severe hypertriglyceridemia as an indication for plasmapheresis. ⋯ Patients with severe hypertriglyceridemia and acute pancreatitis can be conservatively managed safely and effectively without plasmapheresis.