A role for the endothelial glycocalyx in regulating microvascular permeability in diabetes mellitus.
Diabetic angiopathy is a major cause of morbidity and mortality in diabetes mellitus. Endothelial dysfunction and associated alterations in blood flow, pressure and permeability are widely accepted phenomena in the diabetic milieu and are understood to lead to microangiopathy. Despite the clinical importance of diabetic microangiopathy, the mechanisms of pathogenesis remain elusive. In particular, much is yet to be understood about the nature of the putative increased permeability with respect to diabetes. Microvessel permeability is intrinsically difficult to measure and a surrogate (solute or solvent flux) is usually reported, the measurement of which is hampered by haemodynamic factors, such as flow rate, hydrostatic pressure gradient, solute concentration and surface area available for exchange. Very few studies describing the measurement of permeability with respect to diabetes have controlled for all these factors. As a result, the nature of the increased microvessel permeability in diabetes mellitus and indeed its causes are poorly understood. Recent studies have shown that hyperglycaemia can alter the glycocalyx structure, and parallel findings have shown that the apparent increase in permeability demonstrated in hyperglycaemia may be due to an increase in the permeability of the vessels to water, and not an increase in protein permeability, an effect attributable to altered glycocalyx. This review focuses on the current understanding of microvascular permeability in terms of the endothelial glycocalyx-fibre-matrix theory, those methods used to determine permeability in the context of diabetes, and the more recent developments in our understanding of elevated microvascular permeability in the diabetic circulation.
Perrin
Rachel M
RM
Department of Surgery, University of California at Davis Medical Center, Sacramento, CA 95817, USA.
Harper
Steven J
SJ
Bates
David O
DO
D000818:Animals; D002199:Capillary Permeability; D003920:Diabetes Mellitus / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D019276:Glycocalyx / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D049990:Membrane Transport Modulators / Q000378:metabolism; D014867:Water / Q000378:metabolism
D049990:Membrane Transport Modulators; D014867:Water; D005947:Glucose