Endothelial Glycocalyx and Cardiomyocyte Damage Is Prevented by Recombinant Syndecan-1 in Acute Myocardial Infarction

Carl Vahldieck, Eleonora Cianflone, Benedikt Fels, Samuel Löning, Patrik Depelmann, Jolanda Sabatino, Nadia Salerno, Christian M Karsten, Daniele Torella, Joachim Weil, Dong Sun, Michael S Goligorsky, Kristina Kusche-Vihrog

Abstract

The outer layer of endothelial cells (ECs), consisting of the endothelial glycocalyx (eGC) and the cortex (CTX), provides a protective barrier against vascular diseases. Structural and functional impairments of their mechanical properties are recognized as hallmarks of endothelial dysfunction and can lead to cardiovascular events, such as acute myocardial infarction (AMI). This study investigated the effects of AMI on endothelial nanomechanics and function and the use of exogenous recombinant syndecan-1 (rSyn-1), a major component of the eGC, as recovering agent. ECs were exposed in vitro to serum samples collected from patients with AMI. In addition, in situ ECs of ex vivo aorta preparations derived from a mouse model for AMI were employed. Effects were quantified by using atomic force microscopy-based nanoindentation measurements, fluorescence staining, and histologic examination of the mouse hearts. AMI serum samples damaged eGC/CTX and augmented monocyte adhesion to the endothelial surface. In particular, the anaphylatoxins C3a and C5a played an important role in these processes. The impairment of endothelial function could be prevented by rSyn-1 treatment. In the mouse model of myocardial infarction, pretreatment with rSyn-1 alleviated eGC/CTX deterioration and reduced cardiomyocyte damage in histologic analyses. However, echocardiographic measurements did not indicate a functional benefit. These results provide new insights into the underlying mechanisms of AMI-induced endothelial dysfunction and perspectives for future studies on the benefit of rSyn-1 in post-AMI treatment.

Original languageEnglish
JournalAmerican Journal of Pathology
Volume193
Issue number4
Pages (from-to)474-492
Number of pages19
ISSN0002-9440
DOIs
Publication statusPublished - 04.2023

Research Areas and Centers

  • Academic Focus: Center for Infection and Inflammation Research (ZIEL)
  • Centers: Cardiological Center Luebeck (UHZL)

DFG Research Classification Scheme

  • 205-12 Cardiology, Angiology
  • 204-05 Immunology

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