Atorvastatin downregulates HSP22 expression in�an�atherosclerotic model in vitro and in vivo

Abstract

One of the pathological functions of heat shock protein 22 (HSP22) is the association with inflammatory diseases and atherosclerosis. However, the effects of a high-fat diet (HFD) or oxidized low-density lipoprotein (ox-LDL) combined with atorvastatin (ATV) on HSP22 expression are entirely unknown. The present study investigated the effects of ATV on HSP22 expression in HFD-induced atherosclerotic apolipoprotein E-deficient (ApoE−/−) mice and in ox-LDL-induced human umbilical vein endothelial cells (HUVECs). Furthermore, the influence of HSP22-knockdown on the HFD- or ox-LDL-induced atherosclerotic model was also examined. It was found that HFD or ox-LDL treatment significantly increased HSP22 expression in the serum and aorta, accompanied by decreased phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) activity and activated p38 mitogen-activated protein kinase (MAPK). However, these effects were suppressed by treatment with ATV. Furthermore, HSP22-knockdown showed reduced ox-LDL-induced lesions, evidenced by increased p-eNOS activity and inactivated p38 MAPK, while suppression of cell proliferation inhibition and cell cycle arrest were also observed. Taken together, the results of this study suggest that HFD or ox-LDL increased the expression of HSP22 and p-p38 MAPK, and decreased the p-eNOS activity in vitro and in vivo, and ATV could reduce the effects by downregulating HSP22 expression.

Inhibition of microRNA‐103 attenuates inflammation and endoplasmic reticulum stress in atherosclerosis through disrupting the PTEN‐mediated MAPK signaling

“…Although there are many studies on PTEN and AS or MAPK and AS alone (Q. Chen et al, ; F. P. Li et al, ; J. Li et al, ; Ma et al, ; Reustle & Torzewski, ; Wang et al, ), there is no systematic study on the relationship among miR‐103, PTEN and MAPK signaling. Our research explained the relationship between miR‐103, PTEN, MAPK, and ER stress more comprehensively.…”

The Role of HSPB8, a Component of the Chaperone-Assisted Selective Autophagy Machinery, in Cancer

“…This treatment decreases HSPB8 levels and positively correlates with reduced cell proliferation [ 120 ], indicating that AZD8055 is promising for the therapy of tamR BC tumors. Further, the anti-inflammatory statin atorvastatin (ATV) was identified as a negative modulator of HSPB8, both in in vitro and in vivo atherosclerotic models [ 125 , 126 ], but so far has not been tested in BC.…”

Heat Shock Protein 22 in Physiological and Pathological Hearts: Small Molecule, Large Potentials

“…In addition, some HSP22-targeted drugs have also been reported to be beneficial in different diseases and aging. For example, atorvastatin was found to downregulate HSP22 expression in an atherosclerotic model in vitro and in vivo [ 65 ]. Teprenone was also found to increase HSP22 in response to oxidized LDL [ 66 ].…”