Protection against stroke with glucagon-like peptide-1 receptor agonists: a comprehensive review of potential mechanisms

• Published in: Cardiovascular diabetology Vol. 21; no. 1; pp. 242 - 11
• Main Authors: Vergès, Bruno, Aboyans, Victor, Angoulvant, Denis, Boutouyrie, Pierre, Cariou, Bertrand, Hyafil, Fabien, Mohammedi, Kamel, Amarenco, Pierre
• Format: Journal Article
• Language: English
• Published: England BioMed Central 15.11.2022; BMC
• Subjects: Agonists; Angiogenesis; Animal models; Animals; Apoptosis; Arteriosclerosis; Blood pressure; Blood-brain barrier; Brain; Cardiology and cardiovascular system; Clinical trials; Cognitive science; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - chemically induced; Dyslipidemia; Excitotoxicity; GLP-1; Glucagon; Glucagon-like peptide 1; Glucagon-Like Peptide-1 Receptor - agonists; Glucose; Heart failure; Human health and pathology; Humans; Hyperglycemia; Hyperglycemia - chemically induced; Hypoglycemic Agents - adverse effects; Inflammation; Insulin resistance; Ischemia; Life Sciences; Lipoproteins; Mechanisms; Membrane permeability; Metabolism; Neural plasticity; Neurogenesis; Neuroprotection; Neuroscience; Nitric oxide; Oxidative stress; Peptides; Pharmaceutical sciences; Pharmacokinetics; Pharmacology; Review; Risk factors; Smooth muscle; Stroke; Stroke - chemically induced; Stroke - prevention & control; Neuroprotection; Mechanisms; Stroke; GLP-1; Glucagon-like peptide-1 receptor agonists; Hypoglycemic Agents; Hyperglycemia; Animals; Glucagon-Like Peptide-1 Receptor; Humans; Type 2; Diabetes Mellitus
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-022-01686-3

Several randomized controlled trials have demonstrated the benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on ischemic stroke in patients with diabetes. In this review, we summarize and discuss the potential mechanisms of stroke protection by GLP-1RAs. GLP-1RAs exert multiple anti-atherosclerotic effects contributing to stroke prevention such as enhanced plaque stability, reduced vascular smooth muscle proliferation, increased nitric oxide, and improved endothelial function. GLP-1RAs also lower the risk of stroke by reducing traditional stroke risk factors including hyperglycemia, hypertension, and dyslipidemia. Independently of these peripheral actions, GLP-1RAs show direct cerebral effects in animal stroke models, such as reduction of infarct volume, apoptosis, oxidative stress, neuroinflammation, excitotoxicity, blood-brain barrier permeability, and increased neurogenesis, neuroplasticity, angiogenesis, and brain perfusion. Despite these encouraging findings, further research is still needed to understand more thoroughly the mechanisms by which GLP-1RAs may mediate stroke protection specifically in the human diabetic brain.