Update on the Important New Drug Target in Cardiovascular Medicine – the Vascular Glycocalyx

A.      J. Drake-Holland; M.      I.M. Noble

Abstract

We reviewed this subject in 2009, pointing out that, to the process of atherothrombosis, glycocalyx dysfunction and damage must be added to the previous known causitive factors. Glycocalyx dysfunction is possibly the very first step in the process of atherothrombosis, being a protective layer between the endothelial cells and the blood. We emphasise the unique feature of glycocalyx mediated vasodilatation in that it is initiated purely by mechanical changes, i.e., changes in vascular wall shear stress, allowing conduit arteries to adjust diameter to demanded blood flow rate. The predeliction of atheroma to sites of low shear stress, the inhibition of the shear response by lumenal hyperglycaemia, and the fact that the response is mediated by nitric oxide (NO), an anti-atheromatous agent has led to the hypothesis that impairment of this pathway is pro-atherogenic. In the microcirculation it has been shown that the glycocalyx must be added to the factors involved in the Starling hypothesis of tissue fluid generation and exchange. As a consequence glycoalyx dysfunction in hyperglycaemia has been postulated to cause oedema and microalbinuria. We suggested that perhaps the arterial glycocalyx will become the most important for future early prevention of people at risk of cardiovascular disease. The advances in this subject since 2009 are the subject of the present review. What has struck us when searching the literature is that research into the glycocalyx has increased very much and now comes from many disciplines; e.g., diabetes, hypertension, bioengineering, physiology, critical care, cardiology, shock. This update is by no means exhaustive, but hopes, again, to bring to the attention of the pharmaceutical industry, the need for grants in the appropriate experimental models.

Keywords: Diabetes, endothelial vascular injury, inflammatory response, Vascular Glycocalyx, cardiovascular disease, ß-adrenoreceptors

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