High density lipoprotein modulates osteocalcin expression in circulating monocytes: a potential protective mechanism for cardiovascular disease in type 1 diabetes

Cardiovascular Diabetology

Original Investigation

Kyoungmin Park¹  Stephanie D’Eon¹  Qian Li¹  Ronald St-Louis¹  Yu Xia¹  George L. King¹  Liane J. Tinsley¹  Mogher Khamaisi¹  Hillary A. Keenan¹  Ernesto Maddaloni² 

[1] Research Division, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, 02215, Boston, MA, USA;Research Division, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, 02215, Boston, MA, USA;Department of Medicine, Unit of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy;

关键词: Osteocalcin;    Type 1 diabetes;    Cardiovascular disease;    HDL;    Monocytes;    Calcifying monocytes;   

DOI  :  10.1186/s12933-017-0599-2

 received in 2017-04-21, accepted in 2017-09-07,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundCardiovascular 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).MethodsCD45 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.ResultsSubjects 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).ConclusionsLow 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.

【 授权许可】

CC BY   
© The Author(s) 2017