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Updated: Feb 1, 2026
A Human Ex Vivo Atherosclerotic Plaque Model to Study Lesion Biology
Published on: May 6, 2014
Atorvastatin downregulates HSP22 expression in an atherosclerotic model in vitro and in vivo
Qi Chen1, Jian Xiang1, Ren Gong1
1Department of Cardiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Insights
High-fat diets and oxidized LDL increase heat shock protein 22 (HSP22) in atherosclerosis. Atorvastatin (ATV) reduces HSP22 expression, mitigating disease progression by restoring endothelial function.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pathophysiology
Background:
- Heat shock protein 22 (HSP22) is implicated in inflammatory diseases and atherosclerosis.
- The impact of high-fat diets (HFD) and oxidized low-density lipoprotein (ox-LDL) on HSP22 expression, particularly with atorvastatin (ATV) treatment, remains unclear.
Purpose of the Study:
- To investigate the effects of ATV on HSP22 expression in HFD-induced atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice.
- To examine the influence of HSP22 knockdown on HFD- or ox-LDL-induced atherosclerotic models.
- To elucidate the mechanisms underlying ATV's effects on endothelial function and inflammatory pathways.
Main Methods:
- Utilized HFD-induced atherosclerotic ApoE-/- mice and ox-LDL-treated human umbilical vein endothelial cells (HUVECs).
- Administered atorvastatin (ATV) and employed HSP22 knockdown techniques.
- Assessed HSP22 expression, phosphorylated (p)-endothelial nitric oxide synthase (p-eNOS) activity, and p38 mitogen-activated protein kinase (MAPK) activation.
Main Results:
- HFD or ox-LDL significantly increased HSP22 expression, decreased p-eNOS activity, and activated p38 MAPK.
- ATV treatment suppressed these effects, reducing HSP22 levels and improving endothelial function markers.
- HSP22 knockdown attenuated ox-LDL-induced lesions, increased p-eNOS activity, inactivated p38 MAPK, and reversed cell proliferation inhibition and cell cycle arrest.
Conclusions:
- HFD and ox-LDL promote atherosclerosis by upregulating HSP22 and p38 MAPK while downregulating p-eNOS activity.
- ATV exerts protective effects by downregulating HSP22 expression, thereby improving endothelial function and reducing atherosclerotic burden.
- Targeting HSP22 may represent a novel therapeutic strategy for managing atherosclerosis and related inflammatory conditions.
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.
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