In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. suppl_1 ( 2017-05)
Abstract:
Background: Monocytes are critical to the initiation and development of atherosclerosis. To date, 3 distinct human monocyte subsets have been identified based primarily on their expression of the surface markers CD14 and CD16. With the emerging knowledge of myeloid-derived suppressor cells and other myeloid subsets, we hypothesized that monocytes are likely more heterogeneous in composition. Therefore, we set out to use the high dimensionality of mass cytometry to accurately identify and define monocyte subsets in blood of healthy humans and their changes in cardiovascular patients. Methods: Heparinized blood from 12 healthy donors and 15 patients with defined cardiovascular disease (CVD) based on angiography and gensini score was obtained and analyzed by CyTOF mass cytometry. We employed the Phenograph algorithm to cluster and identify all healthy monocyte subsets based on their phenotypes using a 40-marker mass cytometry panel. Results: Phenograph identified a total of 15 monocyte clusters in healthy human blood. By performing hierarchical clustering, we were able to group these clusters into 6 larger meta-clusters and found that most of these meta-clusters fall within the CD14 classical monocyte population, illustrating significant heterogeneity among this monocyte population. Cell numbers of one of these monocyte meta-clusters were significantly increased in blood from patients with CVD. We also identified two subsets of nonclassical monocytes in healthy donors. One of these subsets showed higher expression of the integrin CD61 and tetraspanin CD9, pointing to a possible role for this subset in patrolling and platelet activation. Conclusion: Monocytes are highly diverse with the conventional classical subset showing the most diversity. The numbers and frequencies of some of these monocyte subsets are changed in CVD. Studies to identify their functions in CVD should provide new information for the role of monocytes in CVD.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.37.suppl_1.1
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
1494427-3
