HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content.

High-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (ASCVD), and the magnitude of FC efflux from macrophages to HDL, a metric of HDL function, inversely associated with several metrics of ASCVD. Very high plasma HDL concentrations are associated with increased all-cause and ASCVD mortality, suggesting that the reverse process, FC influx from HDL into macrophages, is atherogenic.

Long-term sustained effects of the Look AHEAD lifestyle intervention on body composition among adults with type 2 diabetes.

Objective: The objective of the study was to test whether there are sustained effects of the Look AHEAD intensive lifestyle intervention (ILI), versus diabetes support and education (DSE), on weight and body composition 12 to 16 years after randomization.

Methods: Participants were a subset of enrollees in the Look AHEAD dual-energy x-ray absorptiometry substudy who completed the final visit, composed of men (DSE = 99; ILI = 94) and women (DSE = 134; ILI = 135) with type 2 diabetes and mean (SD) age 57.2 (6.

The pathophysiology of excess plasma-free cholesterol.

Purpose Of Review: Several large studies have shown increased mortality due to all-causes and to atherosclerotic cardiovascular disease. In most clinical settings, plasma HDL-cholesterol is determined as a sum of free cholesterol and cholesteryl ester, two molecules with vastly different metabolic itineraries. We examine the evidence supporting the concept that the pathological effects of elevations of plasma HDL-cholesterol are due to high levels of the free cholesterol component of HDL-C.

An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

Background: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation.