Canagliflozin attenuates the progression of atherosclerosis and inflammation process in APOE knockout mice

摘要

Sodium glucose co-transporter2 inhibitors reduce the incidence of cardiovascular events in patients with type 2 diabetes mellitus based on the results of recent cardiovascular outcome studies. Herein, we investigated the effects of long-term treatment with canagliflozin on biochemical and immunohistochemical markers related to atherosclerosis and atherosclerosis development in the aorta of apolipoprotein E knockout (Apo-E(?/?)) mice. At the age of 5?weeks, mice were switched from normal to a high-fat diet. After 5?weeks, Apo-E(?/?) mice were divided into control-group (6 mice) treated with 0.5% hydroxypropyl methylcellulose and Cana-group (7 mice) treated with canagliflozin (10?mg/kg per day) per os. After 5?weeks of intervention, animals were sacrificed, and heart and aorta were removed. Sections stained with hematoxylin–eosin (H&E) were used for histomorphometry whereas Masson’s stained tissues were used to quantify the collagen content. Immunohistochemistry to assess MCP-1, CD68, a-smooth muscle actin, MMP-2, MMP-9, TIMP-1 and TIMP-2 expression was carried out and q-PCR experiments were performed to quantify mRNA expression. Canagliflozin-group mice had lower total-cholesterol, triglycerides and glucose levels (P?