Effects of irbesartan on myocardial injury in diabetic rats: The role of NLRP3/ASC/Caspase-1 pathway

Abstract

To observe the mechanism of myocardial injury in diabetic rats after irbesartan intervention and analyze the role of nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) inflammatory pathway. The experiment was divided into four groups: normal control group (CON), high glucose and high caloric diet group (HC), diabetes group (DM) and diabetes+irbesartan group (DM+Ir). Compared with CON group, in HC group, triglyceride, total cholesterol and fasting blood glucose levels were increased; however, there was no significant difference of the cardiac function, the degree of myocardial fibrosis, NLRP3, ASC, Caspase-1 mRNA and protein expressions and the releasing of inflammatory factors interleukin (IL)-1β and IL-18. Compared with HC group, in DM group, triglyceride, total cholesterol, fasting blood glucose, IL-1β and IL-18 levels, NLRP3, ASC, Caspase-1 mRNA and protein expressions and the degree of myocardial fibrosis were increased, but the cardiac function was decreased. Compared with DM group, there were no changes in total cholesterol and fasting blood glucose, the degree of myocardial fibrosis cardiac function was attenuated, NLRP3, ASC, Caspase-1 expressions, IL-1β and IL-18 levels were reduced in DM+Ir group. The results suggested that irbesartan may exert myocardial protection by inhibiting the expression of the NLRP3/ASC/Caspase-1 pathway in diabetic rats.

Changes of Necroptosis in Irbesartan Medicated Cardioprotection in Diabetic Rats

“…Animals were anesthetized with 3% isoflurane (Baxter International, USA), lying supine on a heat pad at 37 degrees Celsius (FUJIFILM VisualSonics, Canada). 8 For stable heart rate image acquisition, the concentration of isoflurane should be further reduced to a minimum of 1–2%. 18 , 19 The left ventricular end-systolic posterior wall thickness, left ventricular end-diastolic posterior wall thickness, end-diastolic diameter (LVEDD), end-systolic inner diameter (LVIDd), percentage of left ventricular Ejection fraction (LVEF%) and percentage of left ventricular fractional shortening (LVFS%) were calculated by the ultrasonic system software.…”

“…[1][2][3] It is closely related to renin-angiotensin system (RAS) activation, microvascular disease, oxidative damage, cardiac inflammation, fibrosis, and apoptosis. [3][4][5][6][7] Ibesartan has been reported to prevent myocardial damage in diabetic rats, 8 however, whether irbesartan can prevent the occurrence of myocardial tissue necrosis has not been reported.…”

NLRP3 Inflammasome Inhibitors in Cardiovascular Diseases

“…Following acute myocardial infarction (AMI), ischemia and the postischemic damage generate DAMPS and the intracellular and extracellular release of alarmins. Moreover, in additional cardiovascular diseases (e.g., atherosclerosis and hypertension) or in chronic disease associated with an increased risk of developing cardiovascular diseases (e.g., obesity or diabetes), priming is promoted by metabolites and/or neurohormonal activation (e.g., angiotensin II, fatty acids, and glucose) [ 38 , 39 , 40 , 41 , 42 , 43 ]. Priming during diabetes increases the expression of components and substrates of the NLRP3 inflammasome, inducing a condition that exacerbates the response to experimental AMI [ 44 ].…”