|
| Effect of mTOR | Study | Animal model | Interventions | Outcomes |
|
| Cardioprotective | Glazer et al. [67] | Transgenic mice | Overexpression of cardiac mTOR | Overexpression of cardiac mTOR reduced mortality in the acute phase and preserved cardiac function in the chronic phase after transient ischemia in vivo |
|
| Cardioprotective | Land and Tee [68] | Transgenic mice | Overexpression of cardiac mTOR | mTOR-Tg mice performed better cardiac function recovery and had less of the necrotic markers CK and LDH subjected to I/R injury in high fat diet-induced obesity |
|
| Cardioprotective | Park et al. [69] | Diabetic mice induced by STZ | Rapamycin (5 mg/kg i.v.) 10 min before I/R | Lin28a overexpression increased p-mTOR and p-p70s6k expression in myocardium exposed to I/R injury in diabetic mice while inhibition of mTOR reduced Lin28a’s cardioprotective effects |
|
| Cardioprotective | Schenkel et al. [70] | C57BL/6 mice | Torin1 (i.p.) immediately after MI with a short 2-day follow-up treatment to inhibit both mTORC1 and mTORC2
Rictor and Raptor siRNA (i.v.) to selectively inhibit mTORC1 or mTORC2
PRAS40 siRNA (i.v.) to inhibit mTOR1 | Inhibition of both mTORC1 and mTORC2 with Torin1 led to increased cardiomyocyte apoptosis and tissue damage after MI. Predominant mTORC1 signaling by suppression of mTORC2 similarly increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. In comparison, preferentially shifting toward mTORC2 signaling by inhibition of mTORC1 with PRAS40 led to decreased cardiomyocyte damage after MI |
|
| Cardioprotective | Tanguy et al. [50] | Neonatal rat ventricular cardiomyocytes | Rapamycin: 50 nM
Adenovirus overexpressing mTOR | Inhibition of mTOR by rapamycin antagonized high glucose-induced inhibition of autophagy and enhanced cardiomyocyte death, while adenovirus-mediated overexpression of mTOR was sufficient to block autophagic flux regardless of glucose concentrations |
|
| Cardioprotective | Rajapakse et al. [71] | Human umbilical vein endothelial cells (HUVECs) | Rapamycin: 25 nM | mTOR activation enhances the activity of HIF1α by inhibiting proteolytic degradation, resulting in elevated VEGF expression |
|
| Cardioprotective | Chong et al. [72] | Human endothelial cells | Rapamycin: 5–10 ng/mL | Loss of mTOR blocks endothelial proliferation and angiogenesis as well as the proliferation of endothelial progenitor cells ex vivo |
|
| Cardiotoxic | Yao et al. [73] | APN knockout mice | Rapamycin (2 mg/kg, i.p.) | Rapamycin reversed APN deficiency-induced drop of fat oxidation in high fat diet feeding |
|
| Cardiotoxic | Si et al. [74] | Transgenic mice | Conditional mTOR knockout mice | Inhibition of mTORC1 reduced endoplasmic reticulum stress, thereby reducing cardiomyocytes death |
|
| Cardiotoxic | Lemaître et al. [75] | CD-1 mice | Rapamycin (0.25 mg/kg, i.p.) | Inhibition of mTOR by rapamycin before ischemia reduced I/R-induced myocardial infarction via activating the JAK2 signal transducer and activator of transcription 3 (STAT3) signaling pathway |
|
| Cardiotoxic | Fourcade et al. [76] | Transgenic mice | Cardiac-specific knockout Raptor to inhibit mTORC1 in vivo | In cardiac mTORC1 disrupted mice, fatty acid oxidation is significantly decreased, whereas glucose oxidation is increased subjected to transverse aortic constriction (TAC) |
|
| Cardiotoxic | Maiese et al. [77] | Male WKY rats and HUVECs | Recombinant adenoviral (rAd) expressing short hairpin RNA (shRNA), S6K1 to inhibit mTORC1 | Inhibition of mTORC1/S6K1 signaling protected endothelial dysfunction related to eNOS uncoupling in vivo and in vitro |
|
| Cardiotoxic | Wang et al. [78] | AMPKα2 knockout mice | Metformin (100 mg/kg/day, gavage) for 3 weeks | Administration of metformin was effective in attenuating TAC-induced LV remodeling in both wild-type and AMPKα2 knockout mice and reduced p-mTOR at Ser2448 and its downstream target p-p70S6K at Thr389 |
|
