Author + information
- Received October 18, 2018
- Revision received October 27, 2018
- Accepted October 29, 2018
- Published online November 5, 2018.
- Daniella C. Terenzi, BHSca,d,
- Mohammed Al-Omran, MD, MScb,d,e,f,
- Adrian Quan, MPhila,
- Hwee Teoh, PhDa,c,
- Subodh Verma, MD, PhDa,d,e,f,∗∗ ( and )
- David A. Hess, PhDb,f,g,∗ ()
- aDivision of Cardiac Surgery
- bDivision of Vascular Surgery
- cDivision of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, ON, Canada
- dInstitute of Medical Science
- eDepartment of Surgery, University of Toronto, Toronto, ON, Canada
- fDepartment of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- gRobarts Research Institute, London, ON, Canada
- ↵∗Address for Correspondence: Dr. David A. Hess, Robarts Research Institute, Western University, 1153 Richmond Street, London, Ontario, Canada, N6A 5B7. Tel: 519-931-5777 x24152
- ↵∗∗Dr. Subodh Verma, Division of Cardiac Surgery, St. Michael’s Hospital, Suite 8-003, 30 Bond Street, Toronto, Ontario, Canada, M5B 1W8. Tel: 416-864-5997.
• This study combined ALDH-activity with cell surface marker expression to develop a multiparametric flow cytometry assay to assess pro-angiogenic progenitor and pro-inflammatory cell content in the peripheral blood of patients with T2D compared to age-matched controls.
• Patients with T2D demonstrated an increased frequency of pro-inflammatory ALDHhi cells with granulocyte side scatter properties and a decreased frequency of circulating monocytes with M2 phenotype that is associated with pro-angiogenic and anti-inflammatory functions.
• Patients with T2D demonstrated significant depletion of circulating pro-vascular ALDHhiCD34+ progenitor cells with primitive, migratory, endothelial, or pericyte phenotypes.
• Sub-group analyses that stratified patients with T2D for age, duration of T2D, insulin requirement, and HbA1C showed that only the duration of T2D correlated with vascular progenitor cell depletion.
• Flow cytometric assessment of circulating ALDHhi cell subsets represents a promising translational approach to identify patients with T2D at increased risk for cardiovascular co-morbidities.
Detection of vascular regenerative cell exhaustion is required to combat ischemic complications during T2D. We used high ALDH-activity and surface marker co-expression to develop a high-throughput flow cytometry-based assay to quantify circulating pro-angiogenic and pro-inflammatory cell content in the peripheral blood of individuals T2D. Circulating pro-angiogenic monocytes expressing anti-inflammatory M2 markers were decreased in patients with T2D. Individuals with longer duration of T2D demonstrated reduced frequencies of circulating pro-angiogenic ALDHhiCD34+ progenitor cells with primitive (CD133) and migratory (CXCR4) phenotype. This approach consistently detected increased inflammatory cell burden and decreased pro-vascular progenitor content in individuals with T2D.
The authors have no financial relationships related to the current work to disclose.
- Received October 18, 2018.
- Revision received October 27, 2018.
- Accepted October 29, 2018.