Atherogenic diet-diminished endothelial glycocalyx contributes to impaired vasomotor properties in rat.

Abstract

Hypercholesterolemia- and atherosclerosis-caused vasomotor property dysfunction may be involved in many clinic manifestations of atherosclerosis, including angina, acute myocardial infarction, and sudden cardiac death. However, its underlying mechanism is not clear. The endothelial glycocalyx is a protective surface layer on the endothelial cells, serving as a molecular sieve, cell adhesion modulator, and mechanosensor for blood flow. In the present study, we demonstrated by confocal microscopy in Sprague-Dawley (SD) male rats fed a 12-wk high-cholesterol diet (HC) compared with the normal diet (NC) that the dimension of the endothelial glycocalyx reduced significantly in both the common carotid artery (2.89 ± 0.41 µm and 3.25 ± 0.44 μm, respectively) and the internal sinus region (2.35 ± 0.07 µm and 3.46 ± 0.86 μm, respectively). Furthermore, we showed by real-time PCR that this dimension modification of endothelial glycocalyx may be attributed to a significant downregulation of heparan sulfate proteoglycan (HSPG)-related genes, including syndecan-3, glypican-1, and EXT1, not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) from the vessel wall to the plasma. Meanwhile, the mean contraction and relaxation forces of the common carotid artery with responses to norepinephrine (NE) and acetylcholine (ACh) decreased ~0.34- and 0.13-fold, respectively, accompanied by a lower level of nitric oxide (NO) release. These findings suggest that the atherogenic high cholesterol diet diminished endothelial glycocalyx and disturbed the local NO release, thus contributing to the impaired vasomotor properties of the vessel.NEW & NOTEWORTHY Twelve-week high-cholesterol (HC) diet reduces the thickness of the endothelial glycocalyx in Sprague-Dawley (SD) male rats, which is mainly attributed to a downregulation of heparan sulfate proteoglycan-related genes (syndecan-3, glypican-1, EXT1), not resulting from an enhanced shedding of sulfated glycosaminoglycans (sGAGs) into the plasma. HC-diminished glycocalyx may disturb its mechanotransduction of local shear stress, lower nitric oxide (NO) release, and impair vasomotor responses to norepinephrine (NE) and acetylcholine (ACh).