期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 22, 期 16, 页码 -出版社
MDPI
DOI: 10.3390/ijms22168786
关键词
sodium-glucose co-transporter 2 inhibitors; diabetes; endothelial dysfunction; cardiovascular disease; neointima formation; arterial stiffness
资金
- American Diabetes Association [1-17-IBS-290]
- University of Missouri School of Medicine TRIUMPH Initiative
SGLT2 inhibitors improve cardiovascular outcomes in patients with diabetes through various mechanisms such as increasing nitric oxide bioavailability, regulating endothelial cell function, and exerting antioxidant and anti-inflammatory effects.
Cardiovascular disease is the leading cause of morbidity and mortality in diabetes. Recent clinical studies indicate that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular outcomes in patients with diabetes. The mechanism underlying the beneficial effect of SGLT2 inhibitors is not completely clear but may involve direct actions on vascular cells. SGLT2 inhibitors increase the bioavailability of endothelium-derived nitric oxide and thereby restore endothelium-dependent vasodilation in diabetes. In addition, SGLT2 inhibitors favorably regulate the proliferation, migration, differentiation, survival, and senescence of endothelial cells (ECs). Moreover, they exert potent antioxidant and anti-inflammatory effects in ECs. SGLT2 inhibitors also inhibit the contraction of vascular smooth muscle cells and block the proliferation and migration of these cells. Furthermore, studies demonstrate that SGLT2 inhibitors prevent postangioplasty restenosis, maladaptive remodeling of the vasculature in pulmonary arterial hypertension, the formation of abdominal aortic aneurysms, and the acceleration of arterial stiffness in diabetes. However, the role of SGLT2 in mediating the vascular actions of these drugs remains to be established as important off-target effects of SGLT2 inhibitors have been identified. Future studies distinguishing drug- versus class-specific effects may optimize the selection of specific SGLT2 inhibitors in patients with distinct cardiovascular pathologies.
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