Vascular Regenerative Cell Exhaustion in Diabetes: Translational Opportunities to Mitigate Cardiometabolic Risk

Daniella C Terenzi; Justin Z Trac; Hwee Teoh; Hertzel C Gerstein; Deepak L Bhatt; Mohammed Al-Omran; Subodh Verma; David A Hess

doi:10.1016/j.molmed.2019.03.006

Vascular Regenerative Cell Exhaustion in Diabetes: Translational Opportunities to Mitigate Cardiometabolic Risk

Trends Mol Med. 2019 Jul;25(7):640-655. doi: 10.1016/j.molmed.2019.03.006. Epub 2019 Apr 30.

Authors

Daniella C Terenzi¹, Justin Z Trac², Hwee Teoh³, Hertzel C Gerstein⁴, Deepak L Bhatt⁵, Mohammed Al-Omran⁶, Subodh Verma⁷, David A Hess⁸

Affiliations

¹ Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A1, Canada.
² Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
³ Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Division of Endocrinology and Metabolism, St. Michael's Hospital Medical Centre, Toronto, ON, M5C 2T2, Canada.
⁴ Division of Endocrinology and Metabolism, McMaster University and Hamilton Health Sciences, Population Health Research Institute, Hamilton, ON, L8S 4K1, Canada.
⁵ Brigham and Women's Hospital, Heart and Vascular Center, Harvard Medical School, Boston, MA 02115, USA.
⁶ Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A1, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada; Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Department of Surgery, University of Toronto, Toronto, ON, M5T 1P5, Canada; Department of Surgery, King Saud University, Riyadh, 11451, Saudi Arabia.
⁷ Division of Cardiac Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, M5 B 1T8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, M5S 1A1, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada; Department of Surgery, University of Toronto, Toronto, ON, M5T 1P5, Canada.
⁸ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada; Division of Vascular Surgery, St. Michael's Hospital, Toronto, ON, M5 B 1W8, Canada; Department of Physiology and Pharmacology, Western University, London, ON, N6A 5C1, Canada; Robarts Research Institute, Western University, London, ON, N6A 5B7, Canada. Electronic address: [email protected].

PMID: 31053416
DOI: 10.1016/j.molmed.2019.03.006

Abstract

Ischemic cardiovascular complications remain a major cause of mortality in people with type 2 diabetes (T2D). Individuals with T2D may have a reduced ability to revascularize ischemic tissues due to abnormal production of circulating provascular progenitor cells. This 'regenerative cell exhaustion' process is intensified by increasing oxidative stress and inflammation and during T2D progression. Chronic exhaustion may be mediated by changes in the bone marrow microenvironment that dysregulate the wingless related integration site network, a central pathway maintaining the progenitor cell pool. Restoration of vascular regenerative cell production by reducing glucotoxicity with contemporary antihyperglycemic agents, by reducing systemic inflammation postbariatric surgery, or by modulating progenitor cell provascular functions using exosomal manipulation, may provide unique approaches for mitigating ischemic disease.

Keywords: bariatric surgery; bone marrow; diabetes; exosomes; inflammation; ischemia; oxidative stress; progenitor cells; revascularization.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Biomarkers
Blood Vessels / metabolism
Blood Vessels / pathology
Bone Marrow
Cardiovascular Diseases / etiology
Cardiovascular Diseases / metabolism
Cardiovascular Physiological Phenomena
Cell Differentiation
Diabetes Mellitus, Type 2 / complications
Diabetes Mellitus, Type 2 / etiology*
Diabetes Mellitus, Type 2 / metabolism*
Diabetes Mellitus, Type 2 / therapy
Disease Susceptibility*
Extracellular Vesicles / metabolism
Humans
Neovascularization, Physiologic*
Obesity / metabolism
Obesity / surgery
Oxidative Stress
Risk
Signal Transduction
Stem Cell Niche
Translational Research, Biomedical

Substances

Biomarkers

Grants and funding

MOP#378189/CIHR/Canada