Atherosclerosis is closely related to the occurrence of cognitive impairment,and diabetes and atherosclerosis are risk factors for it.Therefore,in clinical practice,patients with diabetes mellitus are the high-risk population of atherosclerosis and cognitive impairment.Sodium-glucose cotransporter 2 inhibitor(SGLT2i)is a new type of hypoglycemic drug that has been launched in recent years.Growing evidences have shown the protective effect of SGLT2i on atherosclerosis and nerves via multiple mechanisms,including lowering the pro-inflammatory cytokines,M2 macrophage polarization,inhibiting STAT1 and NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome and reducing oxidative stress.SGLT2i can also improve endothelial function,prevent remodeling,and protect the neurovascular unit,blood-brain barrier,pericytes and oligodendrocytes.SGLT2i is found to significantly upregulate brain-derived neurotrophic factor(BDNF),restore the circadian rhythm of mechanistic target of rapamycin(mTOR)activation,reduce the degree of atherosclerosis,and regulate neurotransmission to ensure the growth,survival and plasticity of neurons.This article reviews the latest progress in the protective mechanism of SGLT2i on atherosclerosis and nerves,thus providing new ideas for further clinical treatment of atherosclerosis,cognitive impairment and other cardiovascular and cerebrovascular diseases.
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