In vivo glycocalyx degradation induces proteinuria and insulin resistance without affecting atherogenesis in apoE knockout mice on a Western-type diet

Abstract

Four weeks of hyaluronidase (HYAL) infusion was used to study the role of the endothelial glycocalyx in vascular circulatory- and barrier properties, and atherogenic lesion progression in apoE knockout (apoE^−/−) mice on a Western-type diet (HFC). Male apoE^−/− on HFC for 10 weeks and Hyal (10 U/hr, i.v. in the last 4 weeks) revealed a significantly reduced systemic endothelial glycocalyx volume of 11.3 ± 7.7 mL/kg BW, compared to pre diet- and Hyal_inactive groups (21.6 ± 6.3 and 17.9 ± 9.8 mL/kg BW, respectively). Red blood cell volume (27.6 ± 4.0 vs. 27.9 ± 1.6 and 30.5 ± 6.0 mL/kg BW, Hyal vs. pre diet and Hyal_inactive, respectively) and hematocrit (0.43 ± 0.03 vs. 0.45 ± 0.02 and 0.41 ± 0.03) were not changed. Hyal infusion induced a significant renal protein leakage (urine protein/creatinin ratio 0.27 ± 0.02 vs. 0.06 ± 0.03 and 0.15 ± 0.01), without changes in renal morphology, and increased insulin resistance (HOMA-IR 6.6 ± 5.7 vs. 1.7 ± 0.1 and 3.3 ± 2.5). There was no effect on atherogenic lesion progression (innominate artery lesion area 14.9 ± 6.2 vs. 0.74 ± 1.0 and 16.4 ± 9.1 x 10,000 µm² ). Our findings indicate that accelerated glycocalyx degradation in an atherogenic mouse model contributes to loss of glycocalyx volume and in turn modest changes in renal function and insulin homeostasis without affecting atherogenesis.

Supported by NHF 2005T037 to H. Vink