High density lipoprotein modulates osteocalcin expression in circulating
monocytes: a potential protective mechanism for cardiovascular disease in type 1
Authors Maddaloni E, Xia Y, Park K, D'Eon S, Tinsley LJ, St-Louis R, Khamaisi M, Li Q,
King GL, Keenan HA
Submitted By Hillary Keenan on 9/25/2017
Status Published
Journal Cardiovascular diabetology
Year 2017
Date Published
Volume : Pages 16 : 116
PubMed Reference 28915881
Abstract Cardiovascular disease (CVD) is a major cause of mortality in type 1 diabetes
(T1D). A pro-calcific drift of circulating monocytes has been linked to vascular
calcification and is marked by the surface expression of osteocalcin (OCN). We
studied OCN+ monocytes in a unique population with =50 years of T1D, the 50-Year
Joslin Medalists (J50M)., CD45 bright/CD14+/OCN+ cells in the circulating
mononuclear blood cell fraction were quantified by flow cytometry and reported
as percentage of CD45 bright cells. Mechanisms were studied by inducing OCN
expression in human monocytes in vitro., Subjects without history of CVD
(n = 16) showed lower levels of OCN+ monocytes than subjects with CVD (n = 14)
(13.1 ± 8.4% vs 19.9 ± 6.4%, p = 0.02). OCN+ monocytes level was inversely
related to total high density lipoprotein (HDL) cholesterol levels (r = -0.424,
p = 0.02), large (r = -0.413, p = 0.02) and intermediate (r = -0.445, p = 0.01)
HDL sub-fractions, but not to small HDL. In vitro, incubation with OxLDL
significantly increased the number of OCN+ monocytes (p < 0.01). This action of
OxLDL was significantly reduced by the addition of HDL in a concentration
dependent manner (p < 0.001). Inhibition of the scavenger receptor B1 reduced
the effects of both OxLDL and HDL (p < 0.05)., Low OCN+ monocytes levels are
associated with lack of CVD in people with long duration T1D. A possible
mechanism for the increased OCN+ monocytes could be the elevated levels of
oxidized lipids due to diabetes which may be inhibited by HDL. These findings
suggest that circulating OCN+ monocytes could be a marker for vascular disease
in diabetic patients and possibly modified by HDL elevation.

Investigators with authorship
Hillary KeenanJoslin Diabetes Center - Boston