Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia

Abstract

The endothelial glycocalyx has been shown to serve as a protective barrier between the flowing blood and the vessel wall in experimental models. The aim of this study was to evaluate whether hypercholesterolemia is associated with glycocalyx perturbation in humans, and if so, whether statin treatment can restore this. We measured systemic glycocalyx volume (V G ) in 13 patients with heterozygous familial hypercholesterolemia (FH) after cessation of lipid-lowering therapy for a minimum of 4 weeks and 8 weeks after initiating rosuvastatin therapy. Normocholesterolemic subjects were used as controls. V G was estimated by subtracting the intravascular distribution volume of a glycocalyx permeable tracer (dextran 40) from that of a glycocalyx impermeable tracer (labeled erythrocytes). V G in untreated FH patients [LDL 225 6 57 mg/dl (mean 6 SD)] was significantly reduced compared with controls (LDL 93 6 24 mg/dl) (V G 0.8 6 0.3 vs. 1.7 6 0.6, respectively, P , 0.001). After normalization of LDL levels (95 6 33 mg/dl) upon 8 weeks of statin treatment, V G recovered only partially (V G 1.1 6 0.4 L, P 5 0.04). The endothelial glycocalyx is profoundly reduced in FH patients, which may contribute to increased atherogenic vulnerability. This perturbation is partially restored upon short-term statin therapy.-Meuwese,

Commentary: On the Pathophysiology of Coronary Heart Disease

“…Consistent with this theory, flow-mediated dilatation is impaired is impaired in patients with coronary disease [8]. There is thinning of the glycocalyx in diabetes [2] and heterozygous familial hypercholesterolemia [9], both diseases characterised by proneness to coronary disease. Constantinescu et al [10] demonstrated thinning of the glycocalyx by oxidised LDL.…”

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

“…[33][34][35] Mean systemic ESL volume in healthy individuals was shown to be 1.5-1.7 L, whereas much lower systemic ESL volumes were found in treated (1.1 L) and untreated (0.8 L) patients with heterozygous familial hypercholesterolemia and normoalbuminuric (0.8 L) and microalbuminuric (0.2 L) patients with type 1 diabetes. 33,34 Elevated shedding products, reflecting ESL breakdown, have been found in patients with severe sepsis, CKD, or ESRD, patients on dialysis, patients after major vascular surgery, and patients during acute or chronic hyperglycemia. 31,33,[35][36][37][38][39][40] Most of these conditions associated with a perturbed ESL are also characterized by an expanded ECV, higher BP, or both, suggesting that variability in sodium homeostasis and salt sensitivity may be related to the quality of the ESL, in which endothelial GAGs act as an intravascular buffer compartment for sodium.…”

“…[30][31][32] Great variability in systemic ESL volume has been reported between different medical conditions, regardless of how ESL volume was estimated. [33][34][35] Mean systemic ESL volume in healthy individuals was shown to be 1.5-1.7 L, whereas much lower systemic ESL volumes were found in treated (1.1 L) and untreated (0.8 L) patients with heterozygous familial hypercholesterolemia and normoalbuminuric (0.8 L) and microalbuminuric (0.2 L) patients with type 1 diabetes. 33,34 Elevated shedding products, reflecting ESL breakdown, have been found in patients with severe sepsis, CKD, or ESRD, patients on dialysis, patients after major vascular surgery, and patients during acute or chronic hyperglycemia.…”

The endothelial glycocalyx: a review of the vascular barrier

“…Rosuvastatin can partially restore glycocalyx volume in familial hypercholesterolaemia. However, it is uncertain whether this was a direct statin effect, or related to the improved lipid status [42].…”