Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction

Area of Science:

• Cardiovascular Science
• Aging Research
• Biomedical Engineering

Background:

• Advanced age is associated with arterial dysfunction and a diminished glycocalyx, potentially due to reduced high molecular weight-hyaluronan (HMW-HA) synthesis.
• The specific impact of glycocalyx deterioration on age-related arterial dysfunction remains largely unknown.
• Investigating the glycocalyx's role is crucial for understanding and treating age-associated vascular changes.

Purpose of the Study:

• To determine if manipulating glycocalyx properties influences arterial function in aging.
• To investigate the potential of glycocalyx-targeted therapies to ameliorate age-related arterial dysfunction.
• To establish the link between glycocalyx integrity and vascular health during aging.

Main Methods:

• Utilized tamoxifen-induced hyaluronan synthase 2 (Has2) reduction in mice to decrease glycocalyx properties.
• Administered a glycocalyx-targeted therapy (Endocalyx™, ECX) containing HMW-HA to aged mice for 10 weeks.
• Supplemented aged mice with HMW-HA alone to compare effects with the ECX therapy.
• Assessed arterial function through endothelium-dependent dilation (EDD) and aortic stiffness measurements.
• Analyzed aortic tissue for collagen and elastin content to evaluate vascular remodeling.

Main Results:

• Has2 reduction mimicked age-related arterial dysfunction, causing lower glycocalyx thickness, impaired EDD, and increased aortic stiffness.
• Treatment with ECX in aged mice significantly improved glycocalyx properties, EDD, and reduced aortic stiffness.
• Aged mice receiving ECX exhibited a more youthful aortic phenotype with decreased collagen and increased elastin content.
• Supplementation with HMW-HA alone yielded similar improvements in glycocalyx properties and arterial function as ECX therapy.
• No significant differences were observed between the ECX and HMW-HA treatment groups.

Conclusions:

• Glicocalyx reduction through Has2 inhibition phenocopies age-related arterial dysfunction.
• Glicocalyx-targeted therapy, including ECX and HMW-HA supplementation, effectively ameliorates age-related arterial dysfunction.
• The findings strongly suggest that the glycocalyx is a viable therapeutic target for mitigating age-related vascular decline.