Endothelial Glycocalyx (EG) injury after Acute Myocardial Infarction (AMI) and its prognostic implications in the control of microvascular coronary flow: EGAMI (Endothelial Glycocalyx in Acute Myocardial Infarction) study and sub-studies

• Grant number: 23/06135-7
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2023
• End date: June 30, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Carlos Henrique Miranda
• Grantee: Carlos Henrique Miranda
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The endothelial glycocalyx (EG) is constituted by proteoglycans (syndecan-1, glypican, CD44) connected to the luminal surface of endothelial cells associated with numerous molecules of glycosaminoglycans (GAGs), such as heparan sulfate, chondroitin sulfate, hyaluronic acid. The EG has several functions, highlighting the control of vascular permeability, control of the adhesion of neutrophils and platelets on the endothelial surface, and signal transduction to release nitric oxide. On the other hand, acute myocardial infarction (AMI) is the leading cause of mortality worldwide, and percutaneous coronary intervention (PCI) is the gold standard treatment. Coronary microvascular compromise is triggered even after the early opening of the occluded or sub-occluded coronary artery responsible for the AMI. The functional and structural obstruction of the coronary microcirculation has an unfavorable impact, worsening the clinical evolution, increasing the AMI extent, and leading to left ventricular remodeling. Endothelial dysfunction is one of the mechanisms involved in this process. We hypothesize that EG injury plays a central role in installing microvascular dysfunction after AMI. Methods: Cross-sectional study followed by a prospective cohort, in which 120 patients with AMI after undergoing PCI will be included. They will be submitted to sublingual videomicroscopy through the Capiscope Video Capillaroscopy System, whose images will be analyzed by the GlycoCheck software, which, among other parameters, estimates the EG thickness. Biomarkers of EG injury (syndecan-1, CD44, hyaluronic acid, heparan sulfate), inflammatory activity (IL-1b, TNF-a), endothelial dysfunction (level of nitrites, thrombomodulin, tissue plasminogen activator) and oxidative stress (TBARS, reduced glutathione, peroxides) will be measured in a blood sample. Patients will be followed for assessment of major cardiovascular events (MACE) during a one-year follow-up. This laboratorial assessment will be repeated in a subgroup of patients (N=20) after six months. In another subset, cardiac magnetic resonance imaging will be performed to assess the extent of coronary microcirculation obstruction. We will also include a translational experimental study to investigate the action of fucoidan, a sulfated polysaccharide obtained from brown seaweed common on the Brazilian coast, in the preservation of EG, in the restoration of flow and coronary microcirculation in an experimental model of myocardial ischemia-reperfusion in an isolated heart of perfused mice. (AU)