Rapamycin: A Bacteria-Derived Immunosuppressant That Has Anti-atherosclerotic Effects and Its Clinical Application

Abstract

Atherosclerosis (AS) is the leading cause of stroke and death worldwide. Although many lipid-lowering or antiplatelet medicines have been used to prevent the devastating outcomes caused by AS, the serious side effects of these medicines cannot be ignored. Moreover, these medicines are aimed at preventing end-point events rather than addressing the formation and progression of the lesion. Rapamycin (sirolimus), a fermentation product derived from soil samples, has immunosuppressive and anti-proliferation effects. It is an inhibitor of mammalian targets of rapamycin, thereby stimulating autophagy pathways. Several lines of evidence have demonstrated that rapamycin possess multiple protective effects against AS through various molecular mechanisms. Moreover, it has been used successfully as an anti-proliferation agent to prevent in-stent restenosis or vascular graft stenosis in patients with coronary artery disease. A thorough understanding of the biomedical regulatory mechanism of rapamycin in AS might reveal pathways for retarding AS. This review summarizes the current knowledge of biomedical mechanisms by which rapamycin retards AS through action on various cells (endothelial cells, macrophages, vascular smooth muscle cells, and T-cells) in early and advanced AS and describes clinical and potential clinical applications of the agent.

Six-Month Outcomes From the First-in-Human, Single-Arm SELUTION Sustained-Limus-Release Drug-Eluting Balloon Trial in Femoropopliteal Lesions

“…3 Rapamycin and its analogues also have documented anti-inflammatory properties that derive from the ability to inhibit reproduction and proliferation of circulating inflammatory cells, in a similar manner as seen with SMCs. 21 Despite the beneficial anti-inflammatory properties and other comparative advantages (wider therapeutic window and a higher safety margin 5,6 ) that have led to rapamycin analogues becoming the preferred coatings for coronary DES, sirolimus and other limus drugs present a challenge when used on balloons. Because tissue bioavailability, which affects both drug uptake and retention, is lower for limus drugs than for paclitaxel, absorption enhancers are required to improve tissue uptake and thereby increase the concentration of the drug in the cells lining the artery wall.…”

Suppression of sirtuin 1 alleviates airway inflammation through mTOR‑mediated autophagy

“…Rapamycin represents a macrolide with known immunosuppressive functions ( 10 ). While rapamycin affects multiple nutrient signaling-associated pathways, it acts mainly as a mammalian target of rapamycin (mTOR) inhibitor, by directly suppressing mTOR complex 1 ( 11 ).…”

Rapamycin: Drug Repurposing in SARS-CoV-2 Infection

“…On one hand, rapamycin is not a virustatic agent, but on the other hand, by focusing on host factors (not on the virus itself), it may represent a better candidate for COVID-19 therapy than commonly tested antivirals. It is also likely that its efficiency will not be reduced by the high rate of viral RNA mutation [ 20 ].…”