Empagliflozin attenuates traumatic brain injury-induced atherosclerosis and norepinephrine-induced vascular smooth muscle cell responses
Abstract
Traumatic brain injury (TBI) is associated with increased long-term cardiovascular risk, but strategies to limit post-traumatic vascular disease are lacking. We tested whether empagliflozin, a sodium-glucose cotransporter 2 inhibitor, attenuates TBI-induced atherosclerosis in apolipoprotein E-deficient mice. Mice on a Western diet underwent controlled cortical impact or sham surgery and received empagliflozin or vehicle for 10 weeks. TBI increased aortic plaque burden, aortic-root lesion size, and blood pressure without changing plasma cholesterol, glucose, insulin, or 8-isoprostane. In vehicle-treated mice plasma norepinephrine was higher after TBI but not significantly elevated in TBI mice treated with empagliflozin. Empagliflozin prevented the TBI-associated increases in blood pressure and atherosclerosis. SGLT2 immunoreactivity was detected in smooth muscle cell-rich plaque regions and in cultured murine vascular smooth muscle cells. In vitro, empagliflozin inhibited norepinephrine-induced smooth muscle cell migration and proliferation. These findings show that empagliflozin attenuates TBI-accelerated atherosclerosis independently of measured systemic metabolic changes. Hemodynamic effects and direct effects on vascular smooth muscle cell responses may contribute to this protection.
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BibTeX
@article{wang2026empagliflozin,
title = {{Empagliflozin attenuates traumatic brain injury-induced atherosclerosis and norepinephrine-induced vascular smooth muscle cell responses}},
author = {Jintao Wang and Enming J. Su and Daniel A. Lawrence and Daniel T. Eitzman},
journal = {Scientific Reports},
year = {2026},
month = oct,
doi = {10.1038/s41598-026-73123-4},
url = {https://www.nature.com/articles/s41598-026-73123-4},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Empagliflozin attenuates traumatic brain injury-induced atherosclerosis and norepinephrine-induced vascular smooth muscle cell responses
AU - Jintao Wang
AU - Enming J. Su
AU - Daniel A. Lawrence
AU - Daniel T. Eitzman
PY - 2026
DA - 2026/10/08
JO - Scientific Reports
DO - 10.1038/s41598-026-73123-4
UR - https://www.nature.com/articles/s41598-026-73123-4
AB - Traumatic brain injury (TBI) is associated with increased long-term cardiovascular risk, but strategies to limit post-traumatic vascular disease are lacking. We tested whether empagliflozin, a sodium-glucose cotransporter 2 inhibitor, attenuates TBI-induced atherosclerosis in apolipoprotein E-deficient mice. Mice on a Western diet underwent controlled cortical impact or sham surgery and received empagliflozin or vehicle for 10 weeks. TBI increased aortic plaque burden, aortic-root lesion size, and blood pressure without changing plasma cholesterol, glucose, insulin, or 8-isoprostane. In vehicle-treated mice plasma norepinephrine was higher after TBI but not significantly elevated in TBI mice treated with empagliflozin. Empagliflozin prevented the TBI-associated increases in blood pressure and atherosclerosis. SGLT2 immunoreactivity was detected in smooth muscle cell-rich plaque regions and in cultured murine vascular smooth muscle cells. In vitro, empagliflozin inhibited norepinephrine-induced smooth muscle cell migration and proliferation. These findings show that empagliflozin attenuates TBI-accelerated atherosclerosis independently of measured systemic metabolic changes. Hemodynamic effects and direct effects on vascular smooth muscle cell responses may contribute to this protection.
SN - 2045-2322
ER -