The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases

Abstract

Purpose In 2007 the two senior authors wrote a review on the structure and function of the endothelial glycocalyx layer (Weinbaum in Annu Rev Biomed Eng 9:121–167, 2007). Since then there has been an explosion of interest in this hydrated gel-like structure that coats the luminal surface of endothelial cells that line our vasculature due to its important functions in (A) basic vascular physiology and (B) vascular related diseases. This review will highlight the major advances that have occurred since our 2007 paper. Methods A literature search mainly focusing on the role of the glycocalyx in the two major areas described above was performed using electronic databases. Results In part (A) of this review, the new formulation of the century old Starling principle, now referred to as the Michel–Weinbaum glycoclayx model or revised Starling hypothesis, is described including new subtleties and physiological ramifications. New insights into mechanotransduction and release of nitric oxide due to fluid shear stress sensed by the glycocalyx are elaborated. Major advances in understanding the organization and function of glycocalyx components, and new techniques for measuring both its thickness and spatio-chemical organization based on super resolution, stochastic optical reconstruction microscopy (STORM) are presented. As discussed in part (B) of this review, it is now recognized that artery wall stiffness associated with hypertension and aging induces glycocalyx degradation, endothelial dysfunction and vascular disease. In addition to atherosclerosis and cardiovascular diseases, the glycocalyx plays an important role in lifestyle related diseases (e.g., diabetes) and cancer. Infectious diseases including sepsis, Dengue, Zika and Corona viruses, and malaria also involve the glycocalyx. Because of increasing recognition of the role of the glycocalyx in a wide range of diseases, there has been a vigorous search for methods to protect the glycocalyx from degradation or to enhance its synthesis in disease environments. Conclusion As we have seen in this review, many important developments in our basic understanding of GCX structure, function and role in diseases have been described since the 2007 paper. The future is wide open for continued GCX research.

Glycocalyx as Possible Limiting Factor in COVID-19

“…Albumin carries sphingosine-1 phosphate to the endothelium, which inhibits syndecan-1 shedding ( 62 ). Further, rhamnan sulfate, a polysaccharide extracted from the green algae M. nitidum has antiviral and antithrombotic properties ( 63 , 64 ). Sevoflurane, which is used during anesthesia, has been shown to be protective against ischemia- reperfusion injury of the glycocalyx ( 65 ).…”

“…Sevoflurane, which is used during anesthesia, has been shown to be protective against ischemia- reperfusion injury of the glycocalyx ( 65 ). Recently, liposomal nanocarriers with pre-assembled glycocalyx have been developed and shown to restore NO- production in heparanase III -treated endothelial cells ( 64 , 66 ). Another therapeutic opportunity includes an anti-adhesive coating of the glycocalyx, consisting of a dermatan sulfate backbone with multiple selectin- binding peptides, which prevents platelet binding to inflamed endothelium ( 67 ).…”

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

“…(Weinbaum et al, 2020) review the role of glycocalyx in various vascular-related diseases and note that the glycocalyx is a target for influenza viruses as well as SARS-COV. They also review a number of therapeutic agents for stabilising the glycocalyx.…”

Special Issue on Professor John M. Tarbell’s Contribution to Cardiovascular Engineering

“…In this Special Issue, Weinbaum, Cancel, and Fu joined with John Tarbell to review their common topic of interests on the glycocalyx. 37 They summarize the current knowledge on the role of endothelial glycocalyx in intercellular interactions and how it is implicated in atherosclerosis and cancer metastasis. The luminal surface of vascular endothelial cells are coated with glycocalyx, which is the hydrated gel-like structure.…”

“…38 In this current issue, we teamed up with Limary Cancel and my City College BME colleague, Bingmei Fu, to present a new and exhaustive review of the glycocalyx. 37 Most of my recent effort at City College has been focused on the glycocalyx. Two of my latest and most productive post docs who studied the glycocalyx while at City have moved on to academic positions and continue studying the glycocalyx.…”