Lovastatin exerts protective effects on endothelial cells via upregulation of PTK2B

Abstract

Statins are HMG-CoA reductase inhibitors that are used to decrease the blood levels of low-density lipoprotein (LDL). In addition, they have been shown to exert pleiotropic protective effects in the absence of LDL-lowering activity. The present study investigated the effects of lovastatin on global gene expression in human umbilical vein endothelial cells (HUVECs), in order to further explore its ability to protect against oxidized (ox)-LDL-induced cytotoxicity. HUVECs were treated with lovastatin for 2–24 h, and gene expression patterns were analyzed using cDNA microarrays. The results suggested that numerous genes were regulated by lovastatin, including certain genes associated with cell survival, such as PTK2B, BCL2 and MAP3K3. In particular, PTK2B, which has been shown to exert anti-apoptotic effects against ox-LDL-induced cell injury, was upregulated by lovastatin. Knockdown of PTK2B was able to attenuate ox-LDL-induced cell injury, and this was associated with decreased levels of phosphorylated-AKT and eNOS, and inhibition of mitochondrial-dependent apoptosis. In conclusion, the results of the present study suggested that lovastatin protects against ox-LDL-induced cell injury, potentially via the upregulation of PTK2B, which regulates the anti-apoptosis signaling pathway.

RNA-seq expression profiling of rat MCAO model following reperfusion Orexin-A

“…Ptk2b can be up-regulated by lovastatin, resulting in an anti-apoptotic effect on ox-LDL-induced cell injury in endothelial cells. The protective effect of Ptk2b is associated with the AKT signalling pathway [ 45 ]. At 24-72 h after focal cerebral ischemia, phospho-Ptk2b was rapidly induced in microglia surrounding the necrotic infarction area, and phospho-Ptk2b was confirmed to colocalise with phospho-p38 and act as an upstream mediator of the p38 signalling pathway after cerebral ischemia [ 46 ].…”

Effects of statins on multispecies oral biofilm identify simvastatin as a drug candidate targeting Porphyromonas gingivalis

“…Decreased amount of these components inhibits post‐translational prenylation of numerous proteins that function as molecular switches . In subjects at risk for cardiovascular disease, statins were also shown to downregulate interleukin (IL)‐8 and IL‐6 production by epithelial cells, reduce the levels of C‐reactive protein in serum, and inhibit oxidized low‐density lipoprotein‐induced cell death . Furthermore, as statins were reported to greatly affect the process of bone regeneration via actions on mesenchymal stem cells, osteoblasts, endothelial cells, and osteoclasts, they sparked significant interest in the fields of tissue regeneration and tissue engineering …”

Impact of Red Yeast Rice on Metabolic Diseases: A Review of Possible Mechanisms of Action

“…The RYR-induced improvement in endothelial cell function may be due to enhancement of the biological activity of NO in endothelial cells by MK through promotion and stabilization of the expression of the endothelial nitric oxide synthase (eNOS) gene and blockage of the uncoupling of eNOS from tetrahydrobiopterin (BH 4 ). Moreover, MK promoted eNOS expression by activating the AKT signaling pathway through focal adhesion kinase 2 (PTK2B) . In addition, MK inhibited the Rho/ROCK pathway and damaged the actin cytoskelecton, resulting in stabilization of eNOS mRNA via mevalonate and geranylgeranyl pyrophosphate (GGPP) .…”

“…MK filled the hydrophobic tunnel through the C-type lectin-like domain (CTLD) of endothelial cell low-density lipoprotein receptor 1 (LOX-1), thereby preventing the specific binding of LOX-1 to ox-LDL . In another study, MK suppressed ox-LDL-induced upregulation of Bcl-associated X protein (BAX) and caspase-3 in the AKT pathway, thereby preventing endothelial cell apoptosis …”