Citation: Sembajwe, L.F.; Ssekandi, A.M.; Namaganda, A.; Muwonge, H.; Kasolo, J.N.; Kalyesubula, R.; Nakimuli, A.; Naome, M.; Patel, K.P.; Masenga, S.K.; et al. Glycocalyx– Sodium Interaction in Vascular Endothelium. Nutrients 2023, 15, 2873. https://doi.org/10.3390/ nu15132873 Academic Editor: Lindsay Brown Received: 20 May 2023 Revised: 19 June 2023 Accepted: 22 June 2023 Published: 25 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). nutrients Review Glycocalyx–Sodium Interaction in Vascular Endothelium Lawrence Fred Sembajwe 1, * , Abdul M. Ssekandi 1 , Agnes Namaganda 1 , Haruna Muwonge 1 , Josephine N. Kasolo 1 , Robert Kalyesubula 1 , Annettee Nakimuli 2 , Mwesigwa Naome 3 , Kaushik P. Patel 4 , Sepiso K. Masenga 5 and Annet Kirabo 3, * 1 Department of Medical Physiology, Makerere University College of Health Sciences, Kampala P.O. Box 7072, Uganda; ssekandi91@gmail.com (A.M.S.); namutoagnes@gmail.com (A.N.); harunamuwonge@gmail.com (H.M.); josephinekasolo57@gmail.com (J.N.K.); rkalyesubula@gmail.com (R.K.) 2 Department of Obstetrics and Gynecology, School of Medicine, Makerere University College of Health Sciences, Kampala P.O. Box 7072, Uganda; annettee.nakimuli@gmail.com 3 Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; mwesigwanaome80@gmail.com 4 Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA; kpatel@unmc.edu 5 Department of Physiological Sciences, School of Medicine and Health Sciences, Mulungushi University, Kabwe P.O. Box 80415, Zambia; sepisomasenga@gmail.com * Correspondence: larryfeds@gmail.com (L.F.S.); annet.kirabo@vumc.org (A.K.) Abstract: The glycocalyx generally covers almost all cellular surfaces, where it participates in me- diating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardio- vascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases. Keywords: endothelial-glycocalyx; proteoglycans; syndecans; hyaluronan; glypicans; sodium chloride-salt; CVD; hypertension 1. Background The blood vascular system consists of a network of vessels ranging from as large as the aorta, arteries, and veins to the smaller units including arterioles, venules, and capillaries [1]. With the exception of the capillaries whose wall is made up of a single layer of endothelial cells, the other vessels have a wall with several tissue layers called tunics: tunica interna, tunica media, and tunica adventitia/externa [2]. The innermost tissue layer in the wall of the blood vessels is the luminal surface layer, consisting of continuously arranged endothelial cells [3]. The single layer of endothelial cells making up the capillaries is interrupted with some fenestrations or pores in some tissues such as in the gastrointestinal tract to enable the transportation of molecules across the capillary wall [3–5]. The luminal surface of endothelial cells is lined with a meshwork consisting of glycoproteins, proteoglycans, and hyaluronic acid/hyaluronan (HA), forming a gel-like material known as the endothelial glycocalyx [6,7]. The main components of the endothelial glycocalyx therefore include Nutrients 2023, 15, 2873. https://doi.org/10.3390/nu15132873 https://www.mdpi.com/journal/nutrients