Oral rapamycin attenuates inflammation and enhances stability of atherosclerotic plaques in rabbits independent of serum lipid levels

Abstract

Background and purpose: Atherosclerotic plaque rupture and thrombosis are the main cause of acute coronary syndrome. The study was aimed to test the hypothesis that oral administration of rapamycin may attenuate inflammation, inhibit progression and enhance stability of atherosclerotic plaques. Experimental approach: Thirty New Zealand rabbits were subjected to balloon-induced endothelial injury of the abdominal aorta and were fed a diet of 1% cholesterol for 20 weeks. From week 9 to week 20, the animals were treated with oral rapamycin (0.5 mg·kg ; group B) and no drugs (group C). At the end of week 20, all rabbits were challenged with injection of Chinese Russell's viper venom and histamine. Serological, ultrasonographic, pathological, immunohistochemical and gene expression studies were performed. Key results: Rapamycin significantly increased the thickness of the fibrous caps and decreased plaque vulnerability index in group A rabbits. Serum lipid levels were higher whereas plaque burden was lower in group A than in group B (P < 0.05). The incidence of plaque rupture in group A (0%) and group B (0%) was significantly lower than that in group C (56.0%, P < 0.05). Conclusions and implications:Oral administration of rapamycin effectively attenuated inflammation, inhibited progression and enhanced stability of atherosclerotic plaques in rabbits, without altering serum lipid levels. Our findings suggest a novel approach to the treatment of atherosclerosis.

Combination of Hydroxyl Acetylated Curcumin and Ultrasound Induces Macrophage Autophagy with Anti-Apoptotic and Anti-Lipid Aggregation Effects

“…With increasing knowledge about therapies targeting atherosclerosis, many studies suggest that the induction of macrophage autophagy plays a protective role in plaque stabilization [34][35][36]. In addition, a growing body of data suggests that autophagy and apoptosis are activated under the same conditions, yet the crosstalk and interplay between them appear to be complex and controversial [37,38].…”

Mammalian target of rapamycin signaling inhibition ameliorates vascular calcification via Klotho upregulation

“…Studies have shown that rapamycin supplementation reduces high-fat diet-induced atherosclerosis in apolipoprotein E-deficient (apoE − / − ) mice, 12 suppresses vascular inflammation, and enhances the stability of atherosclerotic plaques. 13 In addition, rapamycin might be involved in regulating phosphate homeostasis 14 and participate in osteoblastic differentiation. [15][16][17][18] Rapamycin is used as an immunosuppressive agent after kidney transplantation in specific cases, and mTOR signaling inhibition might be associated with renal function reserve in chronic kidney disease (CKD).…”

Virtual Histology Assessment of Cardiac Allograft Vasculopathy Following Introduction of Everolimus—Results of a Multicenter Trial

“…In contrast, we recently demonstrated in the multicenter NOCTET trial (9) that conversion to everolimus and reduced CNI therapy in maintenance HTx patients does not appear to influence CAV progression as quantified by IVUS. Nevertheless, there are experimental and clinical data indicating that PSI agents can effectively attenuate inflammation and inhibit progression and promote stability of atherosclerotic plaques (10,11).…”