OGG1 Preserves Endothelial-Dependent Vasodilation and Regulates the Frequency and Spatial Area of Endothelial Calcium Signals

TL;DR

This study shows that OGG1 helps maintain healthy blood vessel function by regulating calcium signals in endothelial cells and improving blood vessel relaxation.

Contribution

The study reveals a new role for OGG1 in regulating endothelial calcium dynamics and preserving endothelial-dependent vasodilation.

Findings

Mice lacking OGG1 showed increased endothelial calcium signal frequency and area.

Mitochondrial repletion of hOGG1 restored normal calcium signaling and improved vasodilation.

OGG1 is critical for maintaining vascular homeostasis through endothelial calcium regulation.

Abstract

Endothelial calcium dysregulation underlies impairments in endothelial-dependent vasodilation (EDV), contributing to vascular disease progression. Repletion of 8-oxoguanine DNA glycosylase (OGG1), an enzyme involved in base excision repair, has been shown to forestall vascular disease progression. However, the role of OGG1 in regulating endothelial calcium dynamics and in preserving EDV is unknown. Here, calcium imaging via high-speed confocal microscopy and automated analytics was used to quantify the spatial and temporal parameters of endothelial calcium signals in the excised carotid arteries of male and female C57BL6J/FVBNJ mice aged 4–7 months with normal endogenous levels of OGG1, in mice lacking OGG1, and in mice with repleted human OGG1 targeted to the mitochondria. Mice lacking OGG1 exhibited an anomalous calcium phenotype characterized by a substantial increase in the basal tissue-wide frequency and spatial area of the endothelial calcium signals. Mitochondrial repletion of hOGG1 restored the calcium phenotype under unstimulated and acetylcholine-stimulated conditions. EDV was assessed using pressure myography. Mice lacking OGG1 exhibited significant impairments in EDV in response to acetylcholine, and the mitochondrial repletion of OGG1 rescued EDV. These findings highlight a novel role for OGG1 in endothelial signaling and suggest its importance in vascular homeostasis.

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