Lessons from bariatric surgery: Can increased GLP-1 enhance vascular repair during cardiometabolic-based chronic disease?

Abstract

Type 2 diabetes (T2D) and obesity represent entangled pandemics that accelerate the development of cardiovascular disease (CVD). Given the immense burden of CVD in society, non-invasive prevention and treatment strategies to promote cardiovascular health are desperately needed. During T2D and obesity, chronic dysglycemia and abnormal adiposity result in systemic oxidative stress and inflammation that deplete the vascular regenerative cell reservoir in the bone marrow that impairs blood vessel repair and exacerbates the penetrance of CVD co-morbidities. This novel translational paradigm, termed 'regenerative cell exhaustion' (RCE), can be detected as the depletion and dysfunction of hematopoietic and endothelial progenitor cell lineages in the peripheral blood of individuals with established T2D and/or obesity. The reversal of vascular RCE has been observed after administration of the sodium-glucose cotransporter-2 inhibitor (SGLT2i), empagliflozin, or after bariatric surgery for severe obesity. In this review, we explore emerging evidence that links improved dysglycemia to a reduction in systemic oxidative stress and recovery of circulating pro-vascular progenitor cell content required for blood vessel repair. Given that bariatric surgery consistently increases systemic glucagon-like-peptide 1 (GLP-1) release, we also focus on evidence that the use of GLP-1 receptor agonists (GLP-1RA) during obesity may act to inhibit the progression of systemic dysglycemia and adiposity, and indirectly reduce inflammation and oxidative stress, thereby limiting the impact of RCE. Therefore, therapeutic intervention with currently-available GLP-1RA may provide a less-invasive modality to reverse RCE, bolster vascular repair mechanisms, and improve cardiometabolic risk in individuals living with T2D and obesity.

• Authors: Ehab Bakbak, Daniella C Terenzi, Justin Z Trac, Hwee Teoh, Adrian Quan, Stephen A Glazer, Ori D Rotstein, Mohammed Al-Omran, Subodh Verma, David A Hess
• Journal: Reviews in endocrine & metabolic disorders (Rev Endocr Metab Disord) Vol. 22 Issue 4 Pg. 1171-1188 (12 2021) ISSN: 1573-2606 [Electronic] Germany
• PMID: 34228302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Sodium-Glucose Transporter 2 Inhibitors
• Glucagon-Like Peptide 1

Topics

• Bariatric Surgery
• Cardiovascular Diseases (prevention & control)
• Chronic Disease
• Diabetes Mellitus, Type 2 (drug therapy, surgery)
• Glucagon-Like Peptide 1
• Glucagon-Like Peptide-1 Receptor (agonists, therapeutic use)
• Humans
• Hypoglycemic Agents (therapeutic use)
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)