NYMC Faculty Publications

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

Carl Vahldieck, Institute of Physiology, University of Luebeck, Luebeck, Germany; Department of Anesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein Campus Luebeck, University of Luebeck, Luebeck, Germany. Electronic address: carl.vahldieck@uksh.de.
Eleonora Cianflone, Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.
Benedikt Fels, Institute of Physiology, University of Luebeck, Luebeck, Germany; DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg/Luebeck/Kiel, Luebeck, Germany.
Samuel Löning, Institute of Physiology, University of Luebeck, Luebeck, Germany.
Patrik Depelmann, Institute of Physiology, University of Luebeck, Luebeck, Germany.
Jolanda Sabatino, Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy; Division of Pediatric Cardiology, Department of Women's and Children's Health, University Hospital Padua, Padua, Italy; Pediatric Research Institute "Città della Speranza", Padua, Italy.
Nadia Salerno, Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.
Christian M. Karsten, Institute for Systemic Inflammation Research, University of Luebeck, Luebeck, Germany.
Daniele Torella, Department of Experimental and Clinical Medicine, University Magna Græcia of Catanzaro, Catanzaro, Italy.
Joachim Weil, Medizinische Klinik II, Sana Kliniken Luebeck, Luebeck, Germany.
Dong Sun, Renal Research Institute and Departments of Medicine, Pharmacology and Physiology, New York Medical College, Valhalla, New York.
Michael S. Goligorsky, Renal Research Institute and Departments of Medicine, Pharmacology and Physiology, New York Medical College, Valhalla, New York.
Kristina Kusche-Vihrog, Institute of Physiology, University of Luebeck, Luebeck, Germany; DZHK (German Research Centre for Cardiovascular Research), Partner Site Hamburg/Luebeck/Kiel, Luebeck, Germany.

Author Type(s)

Faculty

Journal Title

The American Journal of Pathology

First Page

474

Last Page

492

Document Type

Article

Publication Date

4-1-2023

Department

Physiology

Second Department

Medicine

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.

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