Role of S100A8/A9 in hyperglycemia-associated monocytosis in diabetic subjects

Grants and Contracts Details

Description

Title: Role ofS100A8/A9 in byperglycemia·associated monocytosis in diab etic subjects Rationale: Diabetes is a major risk factor for coronary artery disease (CAD) although the reasons for this remain unclear. Elevated white blood cell counts (WBCs), particularly monocytes and neutrophils are well· known risk factors as well as markers of inflammation and may have a causative role in CAD. We have studied factors that regulate leukocytosis primarily in mouse models of type I diabetes (rID) and found that hyperglycemia, independent of hyperlipidemia promotes monocytosis and neutrophilia. Further, we identified two damage associated molecular patterns (DAIvIPs), S100A8 and S100A9 that are increased in neutrophils in response to hyperglycemia and promotes leukocytosis by acting directly on hematopoictic progenitor cells in the bone marrow (BM). Enhanced myelopoiesis results in increased fotmation of Ly6~ monocytes, a subset of pro--inflammatory monocytes that readily enter lesions and impair atherosclerosis lesion regression (In revision, Nature Medicine). Although our mouse studies establish a connection between elevated plasma levels ofSl 00A8/A9 with monocytosis and defective lesion regression, it is not clear if these observations are translatable to humans. In an effort to study these mechanisms in hwnans, we intend to examine if plasma levcls of S100A8/A9 correlates with monocytosis and HblAclblood glucose in type 2 diabetic (T2D) subjects. We intend to study these pathways in TlD patients for two reasons, I) Majority of the diabetic patients are 1'20 and 2) All TID patients are under insulin therapy and it is unethical to srudy these patients without insulin even for a short period of time.
StatusFinished
Effective start/end date7/1/135/31/14

Funding

  • Canadian Diabetes Association: $35,712.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.