Canagliflozin improves coronary microvascular vasodilation and increases absolute blood flow to the myocardium independent of angiogenesis.
Publication/Presentation Date
8-19-2023
Abstract
OBJECTIVES: Sodium-glucose cotransporter-2 (SGLT-2) inhibitor, canagliflozin (CAN), improves myocardial perfusion to ischemic territory without accompanying changes in vascular density. We aimed to (1) characterize effects on angiogenic pathways, (2) utilize multiomics to identify gene expression and metabolite profiles relevant to regulation of myocardial blood flow, and (3) investigate drug effect on coronary microvascular reactivity.
METHODS: A nondiabetic swine model of chronic myocardial ischemia and nondiabetic rat model were used to study functional and molecular effects of CAN on myocardium and in vitro microvascular reactivity.
RESULTS: CAN resulted in increased coronary microvascular vasodilation and decreased vasoconstriction (p0.3). Expression of angiogenic modulator, endostatin, increased (p = 0.008), along with its precursor, collagen 18 (p
CONCLUSION: In chronic myocardial ischemia, CAN increased absolute blood flow to the myocardium without robustly increasing vascular density or proangiogenic signaling. CAN resulted in altered coronary microvascular reactivity to favor vasodilation, likely through direct effect on vascular smooth muscle. Downregulation of cardiac RAS demonstrated local regulation of perfusion.
ISSN
1097-685X
Published In/Presented At
Banerjee, D., Sabe, S. A., Xing, H., Xu, C., Sabra, M., Harris, D. D., Broadwin, M., Abid, M. R., Usheva, A., Feng, J., & Sellke, F. W. (2023). Canagliflozin improves coronary microvascular vasodilation and increases absolute blood flow to the myocardium independent of angiogenesis. The Journal of thoracic and cardiovascular surgery, S0022-5223(23)00729-8. Advance online publication. https://doi.org/10.1016/j.jtcvs.2023.08.017
Disciplines
Medicine and Health Sciences
PubMedID
37604273
Department(s)
Department of Surgery, Fellows and Residents
Document Type
Article