Assessing Sex Differences in Metabolic Disease on Vasculopathy Using the Vascular Health Index

Introduction: Vascular function with elevated disease risk has been long studied. However, understanding integrated vascular health has been challenging, as most work focuses on specific outcomes, interventions or mechanistic links. While these efforts have revealed factors contributing to vasculopathy, comparing results across laboratories, models and conditions to understand vascular health status remains challenging. Methods: Utilizing the Vascular Health Index (VHI), a validated metric allowing simultaneous assessment of vascular reactivity, wall mechanics and microvessel density within cerebral and skeletal muscle networks, we focus on the impact of metabolic disease risk between male and female obese Zucker rats (OZR). In addition, we study VHI in female OZR following ovariectomy (OVX), with outcomes compared to “healthy” lean Zucker rats (LZR). Results: Male and female LZR demonstrated comparable VHI, although metabolic disease reduced both skeletal muscle and cerebral VHI in male OZR more severely than females. VHI protection for female OZR was dependent on sex hormone cycling, as OVX in female OZR removed protection in VHI versus female OZR. Conclusion: These results indicate that sex-based protections in peripheral and cerebral vascular health with metabolic disease in female OZR are present at multiple levels of resolution and are dependent on normal sex hormone cycling.