Kruppel-like factor 10 (KLF10) as a biomarker of endothelial progenitor cell dysfunction
The use of Kruppel-like Factor (KLF10) as a diagnostic and prognostic tool for peripheral artery disease and other disease conditions associated with reduced angiogenesis or endothelial progenitor cell dysfunction such as diabetes and stent thrombosis.
1. A method of diagnosing and treating peripheral artery disease (PAD) in a subject, the method comprising:
isolating CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject by flow cytometry;
performing an assay to determine a level of Krüppel-like Factor (KLF 10) expression in a sample comprising the peripheral blood cells;
comparing the level of KLF10 in the sample to a reference level of KLF 10;
identifying a subject who has a level of KLF 10 in the sample below the reference level as having PAD; and
administering a treatment for PAD to the identified subject who has a level of KLF10 in the sample that is below the reference level, wherein the treatment comprises a lipid-lowering agent.
2. A method of diagnosing and treating diabetic vasculopathy in a subject with diabetes, the method comprising:
isolating CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject by flow cytometry;
performing an assay to determine a level of Krüppel-like Factor (KLF10) expression in a sample comprising the peripheral blood cells;
comparing the level of KLF10 in the sample to a reference level of KLF10;
identifying a subject who has a level of KLF10 in the sample below the reference level as having diabetic vasculopathy; and
administering a treatment for diabetic vasculopathy to the identified subject who has a level of KLF10 in the sample that is below the reference level, wherein the treatment comprises an angiotensin-converting enzyme (ACE) inhibitor.
3. The method of claim 2 , wherein the subject has type 2 diabetes.
4. The method of claim 1 , further comprising
performing an assay to determine a level of KLF10 expression in a subsequent sample comprising CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject; and
comparing the level of KLF10 in the subsequent sample to the level of KLF10 in the earlier sample;
wherein an increase in a level of KLF10 in the subsequent sample as compared to the earlier sample indicates that the treatment is effective.
5. The method of claim 2 , further comprising
performing an assay to determine a level of KLF10 expression in a subsequent sample comprising CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject; and
comparing the level of KLF10 in the subsequent sample to the level of KLF10 in the earlier sample;
wherein an increase in a level of KLF10 in the subsequent sample as compared to the earlier sample indicates that the treatment is effective.
6. The method of claim 1 , wherein the level of KLF10 expression in the sample is determined by quantitative PCR, flow cytometry, or quantitative immunoassay.
7. The method of claim 2 , wherein the level of KLF10 expression in the sample is determined by quantitative PCR, flow cytometry, or quantitative immunoassay.
8. A method of diagnosing and treating stent thrombosis in a subject with a stent, the method comprising:
isolating CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject by flow cytometry;
performing an assay to determine a level of Krüppel-like Factor (KLF10) expression in a sample comprising the peripheral blood cells;
comparing the level of KLF10 in the sample to a reference level of KLF10;
identifying a subject who has a level of KLF10 in the sample below the reference level as having stent thrombosis; and
administering a treatment for stent thrombosis to the identified subject who has a level of KLF10 in the sample that is below the reference level, wherein the treatment comprises dual anti-platelet therapy.
9. The method of claim 8 , further comprising
performing an assay to determine a level of KLF10 expression in a subsequent sample comprising CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject; and
comparing the level of KLF10 in the subsequent sample to the level of KLF10 in the earlier sample;
wherein an increase in a level of KLF10 in the subsequent sample as compared to the earlier sample indicates that the treatment is effective.
10. The method of claim 8 , wherein the level of KLF10 expression in the sample is determined by quantitative PCR, flow cytometry, or quantitative immunoassay.
11. The method of claim 1 , wherein the lipid-lowering agent is a statin, fibrate, or niacin.
12. A method of diagnosing and treating stent thrombosis in a subject with a stent, the method comprising:
isolating CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject by flow cytometry;
performing an assay to determine a level of Krüppel-like Factor (KLF10) expression in a sample comprising the peripheral blood cells;
comparing the level of KLF10 in the sample to a reference level of KLF10;
identifying a subject who has a level of KLF10 in the sample below the reference level as having stent thrombosis; and
administering a treatment for stent thrombosis to the identified subject who has a level of KLF10 in the sample that is below the reference level, wherein the treatment comprises anti-coagulation therapy.
13. The method of claim 12 , further comprising
performing an assay to determine a level of KLF10 expression in a subsequent sample comprising CD34 + /VEGFR2 + pro-angiogenic peripheral blood cells from the subject; and
comparing the level of KLF10 in the subsequent sample to the level of KLF10 in the earlier sample;
wherein an increase in a level of KLF10 in the subsequent sample as compared to the earlier sample indicates that the treatment is effective.
14. The method of claim 12 , wherein the level of KLF10 expression in the sample is determined by quantitative PCR, flow cytometry, or quantitative immunoassay.