Monocytes and Macrophages as Protagonists in Vascular Complications of Diabetes.
Authors Kanter JE, Hsu CC, Bornfeldt KE
Submitted By Jenny Kanter on 3/31/2020
Status Published
Journal Frontiers in cardiovascular medicine
Year 2020
Date Published
Volume : Pages 7 : 10
PubMed Reference 32118048
Abstract With the increasing prevalence of diabetes worldwide, vascular complications of
diabetes are also on the rise. Diabetes results in an increased risk of
macrovascular complications, with atherosclerotic cardiovascular disease (CVD)
being the leading cause of death in adults with diabetes. The exact mechanisms
for how diabetes promotes CVD risk are still unclear, although it is evident
that monocytes and macrophages are key players in all stages of atherosclerosis
both in the absence and presence of diabetes, and that phenotypes of these cells
are altered by the diabetic environment. Evidence suggests that at least five
pro-atherogenic mechanisms involving monocytes and macrophages contribute to the
accelerated atherosclerotic lesion progression and hampered lesion regression
associated with diabetes. These changes include (1) increased monocyte
recruitment to lesions; (2) increased inflammatory activation; (3) altered
macrophage lipid accumulation and metabolism; (4) increased macrophage cell
death; and (5) reduced efferocytosis. Monocyte and macrophage phenotypes and
mechanisms have been revealed mostly by different animal models of diabetes. The
roles of specific changes in monocytes and macrophages in humans with diabetes
remain largely unknown. There is an ongoing debate on whether the changes in
monocytes and macrophages are caused by altered glucose levels, insulin
deficiency or insulin resistance, lipid abnormalities, or combinations of these
factors. Current research in humans and mouse models suggests that reduced
clearance of triglyceride-rich lipoproteins and their remnants is one important
mechanism whereby diabetes adversely affects macrophages and promotes
atherosclerosis and CVD risk. Although monocytes and macrophages readily respond
to the diabetic environment and can be seen as protagonists in
diabetes-accelerated atherosclerosis, they are likely not instigators of the
increased CVD risk.