Oral rapamycin inhibits growth of atherosclerotic plaque in apoE knock-out mice

Oral rapamycin attenuates atherosclerosis without affecting the arterial responsiveness of resistance vessels in apolipoprotein E-deficient mice

“…There is a consensus that rapamycin significantly reduces the aortic atherosclerotic plaque in apoE-deficient mice fed a fat-rich diet (12,13,22,23,26). In the present study, we also observed similar anti-atherosclerotic effects of rapamycin administered to the apoE-deficient mice fed a normal rodent diet.…”

“…In contrast, Neto et al (11) showed that orally administered rapamycin at the same dose and for the same treatment duration did not affect the vascular tone of Wistar rats. Alternatively, studies on mice have been limited to the evaluation of the effects of rapamycin on the progression of atherosclerotic plaque in apolipoprotein E (apoE) knockout mice fed a high-cholesterol diet (12,13). However, we should consider the physiological importance of studying the effect of this drug on the responsiveness of resistance vessels and on atherosclerosis in this murine model of spontaneous atherosclerosis without the perturbation caused by a supplemented high-fat diet.…”

Autophagy in Vascular Disease

“…Administration of rapalogs in mouse or rabbit models of atherosclerosis, either orally or subcutaneously, results in a marked reduction of both plaque size and plaque complexity despite severe hypercholesterolemia. [96][97][98][99][100][101][102][103][104][105] Indeed, rapalogs can prevent accumulation of macrophages and lipids and reduce cell proliferation and intraplaque angiogenesis via mTOR inhibition. 48 However, it is currently not known whether autophagy is involved in these plaque-stabilizing effects.…”

Rapamycin activates autophagy in Hutchinson-Gilford progeria syndrome

“…In three separate studies involving apoE knockout mice or LDLR knockout mice, rapamycin reduces arteriosclerotic lesions despite the severe hypercholesterolemia in these mice, even when fed a high-fat diet. [29][30][31] Because the cardiovascular disease component of HGPS leads to devastating heart attacks or strokes, it will be of interest to examine if rapamycin confers any benefit on the cardiovascular aspects of HGPS by promoting clearance of progerin in cardiovascular tissues. The G608G mouse model of HGPS has a cardiovascular phenotype that shows improvement with FTI treatment.…”