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.
Status | Finished |
---|---|
Effective start/end date | 7/1/13 → 5/31/14 |
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.