TABLE 1.
Targeted drugs of PI3K and its signaling pathway in atherosclerosis.
| References | Signaling pathways | Target drugs | Effect |
|---|---|---|---|
| Endothelial cell | |||
| Zhou et al. (2018) | PI3K/Akt/NF-κB | Total saponins | Inhibit inflammation |
| Palomo et al. (2020) | PI3K/Akt | Defibrotide | Hinder endothelial cell transformation into proinflammatory phenotypes |
| Kim et al. (2015) | PI3K/Akt | Retinoic acid | Inhibit inflammation by regulating AMPK |
| Liu et al. (2015) | PI3K/Akt | Ginkgolide B | Reduce the permeability of the vascular wall |
| Fu et al. (2013) | PI3K/AKT/eNOS | XJP-1 | Protect against ox-LDL-induced cytotoxicity and apoptosis |
| Chen et al. (2019) | PI3K/AKT/eNOS | CTRP3 | Mediate the inhibition of ox-LDL |
| Nana et al. (2015) | PI3K/AKT/eNOS | Reverse-D-4F | Restore TNF-α-induced endothelial progenitor cell dysfunction |
| Lu et al. (2014) | PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 | Andrographolide | Increase glutathione levels and inhibit ICAM-1 expression |
| Gu et al. (2019) | PI3K/Akt/Nrf2 | Lunasin | Attenuate oxidative-induced endothelial injury |
| Peng et al. (2017) | PI3K/AKT/IRF1 | Thymic stromal lymphopoietin | Regulate EC proliferation and migration |
| Song et al. (2020) | PI3K/Akt/Bad | Gypenosides | Regulate mitochondrial-mediated apoptosis |
| Fu et al. (2019) | PI3K/AKT/FOXO3A | Scutellarin | Inhibit vascular endothelial cell injury and apoptosis |
| Lin et al. (2015) | III PI3K/Beclin-1 and PTEN/PI3K/Akt | Gossyphenol | Improve atherosclerotic lesions and ox-LDL-induced endothelial injury |
| Che et al. (2017) | PI3K/Akt/mTOR | Kaempferol | Enhance autophagy and inhibit ox-LDL-induced apoptosis |
| Smooth muscle cell | |||
| Tang et al. (2015) | PI3K/AKT/Runx2 | VPO1 inhibitor | Hinder ox-LDL-induced vascular calcification |
| Zhan et al. (2015) | PI3K/Akt/mTOR/S6K1 | Lilaru peptide | Inhibit osteogenic differentiation and the calcification |
| Xie et al. (2011) | PI3K/AKT | Omentin-1 | Stimulate OPG expression and inhibit the production of RANKL |
| Ponnusamyet al. (2018) | PI3K/AKT | FTI-277 | Prevent vascular calcification |
| Dong et al. (2018) | PI3K/Akt/mTOR | CTRP6 | Inhibit PDGF-BB-induced proliferation and migration |
| Wang et al. (2016) | PI3K/AKT | Epac1 inhibitor | Inhibit neointimal formation |
| Pantan et al. (2016) | PI3K/AKT | atorvastatin and cyanidin-3-glucoside | Improves HASMC proliferation and migration |
| Shin et al. (2018) | PI3K/Akt/NF-κB | Mulberry pigment | Inhibit the activity of PDGF-induced MMP-9 |
| Lee et al. (2009) | PI3K/AKT/mTOR/p70S6K | Naringin | Inhibit the expression of TNF-α-induced MMP-9 |
| Park et al. (2008) | PI3K/AKT/mTOR/p70S6K | Rosiglitazone | Inhibit insulin-stimulated proliferation |
| Wu W. et al. (2019) | IGF-1R/PI3K/Akt | Overexpression of miR-223 | Induce autophagy and inhibit the formation of foam cells |
| Wu Y. T. et al. (2019) | IGF-1R/PI3K | Tanshinone I | Inhibit vascular smooth muscle cell proliferation |
| Kou et al. (2014) | IGF-1R/Akt/mTOR/p70S6K | Dopamine D1-like receptor | Inhibit vascular smooth muscle cell proliferation |
| Macrophage | |||
| Wu et al. (2020) | PI3K/Akt/mTOR | miR-135b | Enhance macrophage autophagy |
| Han et al. (2019) | PI3K/Akt/mTOR | PDT | Reduce inflammation and increase plaque stability |
| Han et al. (2017) | PI3K/Akt/mTOR | Photodynamic therapy | Promote cholesterol efflux by inducing autophagy |
| Zheng et al. (2020) | PI3K/AKT/TLR4 | GYY4137 | Improve foam cell formation and reduce the expression of proinflammatorycytokines |
| Wang et al. (2020) | PI3K/AKT/TLR4/NF-κB | Tanshinone IIA and Astragaloside IV | Inhibit the expression of MMP-9, stabilize plaque and anti-inflammatory |
| Endale et al. (2013) | PI3K/AKT/TLR4/NF-κB | Quercetin | Attenuate the inflammatory response |
| Wang J. et al. (2015) | PI3K/AKT/TLR4/NF-κB | miR-223 | Reverse macrophage-mediated lipid deposition and the inflammatory response |
| Luo et al. (2015) | PI3K/AKT/Nrf2 | Isorhamnetin | Increase the expression of HO-1 and reduce the level of ROS |
| Kuang et al. (2017) | PI3K/PKCζ/Sp1 | HSP 27 | Promote the outflow of macrophage cholesterol |
| Xu X. et al. (2019) | PI3K/Akt | Naringenin | Promote macrophage cholesterol efflux |
| Fougerat et al. (2008) | PI3K/Akt | PI3K P110γ deletion | Attenuate the inflammatory response |
| Jamuna et al. (2019) | III PI3K/Beclin-1 | OPC and EGCG | Promote cholesterol efflux in macrophage foam cells |
| Matsuo et al. (2015) | PTEN/PI3K/Akt | ARIA | Reduce the expression of ACAT-1 and the formation of foam cells |
| Ong et al., 2019) | PI3K/JNK | Lauric acid | Interfere with the expression of thrombospondin motifs |
| Immune cells and immune inflammation | |||
| Liu et al. (2020) | PI3K/Akt/mTOR | Lymphocyte-specific protein tyrosine kinase inhibitors | Reduce Th1/Treg ratio and inflammatory response |
| Lin et al. (2017) | Dab2/Src/PI3K/Akt/NF-κB | Quercetin | Attenuate DC activation |
| He et al. (2016) | PI3K/AKT/NF-κB/NLRP | Saikosaponin-a | Anti-immune inflammatory response |
| Platelet | |||
| Song et al. (2014) | PI3K/Akt/eNOS/NO/cGMP | Anthocyanins | Inhibit MAPK activation in platelets |
| Moraes et al. (2013) | PI3K/Akt | Statins | Inhibit platelet activation |
| Wang et al. (2018) | PI3K/Akt/mTOR | ROS inhibitors | Inhibit platelet autophagy and alleviate platelet aggregation |
| Myocardial infarction | |||
| Nagaoka et al. (2015) | PI3K/Akt | Nanoparticle-mediated pitavastatin | Protect the myocardium |
| Arslan et al. (2013) | PI3K/Akt | Mesenchymal stem cell-derived exocrine | Enhance myocardial activity |
| Mahajan et al. (2018) | PI3K/Akt/GSK-3β | Eplerenone | Reduce myocardial infarction |
| Younis et al. (2020) | PI3K/Akt/mTOR | Geraniol | Regulate autophagy to reduce oxidative stress |
| Bai et al. (2019) | PI3K/Akt/eNOS | Baicalin | Reduce ischemia/reperfusion injury |
| Sumi et al. (2007) | PI3K/Akt/eNOS | rHDL | Promote ischemic disease-induced angiogenesis |