Key result
Endothelial cell-specific TERT knockout in mice significantly reduced flow-mediated dilation and triggered a pathological switch from nitric oxide-mediated to hydrogen peroxide-mediated dilation.
p-value: p=<0.05
Endothelial-specific TERT deletion in mice is sufficient to cause microvascular endothelial dysfunction and a pathological switch to H2O2-mediated dilation, mimicking the phenotype seen in coronary artery disease.
Endothelial TERT loss switches microvascular dilation to H2O2 in mice; leaves open its role in human coronary endothelial dysfunction.
Previously established by Ait-Aissa et al. (Ait-Aissa K, Kadlec AO, Hockenberry J, Gutterman DD, Beyer AM. Am J Physiol Heart Circ Physiol 314: H1053–H1060, 2018), systemic TERT KO mice have a loss of NO synthase-mediated dilation to flow, accompanied by compensatory increased release of flow-induced H 2 O 2 in coronary and peripheral microcirculations. Our study demonstrates that mice with EC-specific TERT KO exhibit phenotypes similar to systemic TERT deficiency and microvascular pathologies observed in patients with CAD. These findings underscore the critical, noncanonical, and likely mitochondrial-mediated regulation of vascular tone and systemic cardio-metabolic changes.
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Birch et al. (2025) studied Microvascular endothelial dysfunction (n=25). Endothelial cell-specific TERT knockout vs. Cre- control mice was evaluated on Flow-mediated dilation (FMD) in mesenteric arteries (p=<0.05). Endothelial cell-specific TERT knockout in mice significantly reduced flow-mediated dilation and triggered a pathological switch from nitric oxide-mediated to hydrogen peroxide-mediated dilation.
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