Aspirin ameliorates cerebral infarction through regulation of TLR4/NF‑κB‑mediated endoplasmic reticulum stress in mouse model

Abstract

Cerebral infarction is a cerebrovascular disease caused by local brain ischemic necrosis or softening, which is associated with diabetes, obesity, hypertension and rheumatic heart arrhythmia. Previous studies have indicated that aspirin is a potential oral anticoagulant in the treatment of cerebral ischemic stroke. However, the potential mechanism mediated by aspirin in cerebral infarction therapy is not well understood. The present study analyzed the therapeutic effects of aspirin on cerebral infarction and investigated the underlying molecular mechanism of aspirin‑ameliorated benefits for thrombolysis. The results demonstrated that aspirin inhibited inflammation and apoptosis of cerebrovascular endothelial cells in a mouse model of cerebral infarction. Aspirin treatment suppressed toll‑like receptor (TLR)4 and nuclear factor (NF)‑κB expression in cerebrovascular endothelial cells. Endoplasmic reticulum (ER) stress was suppressed by aspirin treatment through the downregulation of protein kinase R‑like endoplasmic reticulum kinase, eukaryotic translation initiation factor 2 subunit 1 and C/EBP homologous protein expression levels in cerebrovascular endothelial cells. It was identified that knockdown of TLR4 inhibited aspirin‑mediated downregulation of NF‑κB signaling pathway and ER stress in cerebrovascular endothelial cells. Expression levels of adenosine diphosphate plasminogen activator inhibitors, von Willebrand factor and thromboxane were downregulated in cerebrovascular endothelial cells and in serum in experimental mice. The results demonstrated that aspirin was beneficial forthrombolysis by decreasing thrombin‑activatable fibrinolysis inhibitor and plasminogen activator inhibitor‑1 expression in a mouse model of cerebral infarction. These results suggested that aspirin may improve cerebral infarction by downregulating TLR4/NF‑κB‑mediated ER stress in a mouse model.

Alterations of protein expression of phospholamban, ZASP and plakoglobin in human atria in subgroups of seniors

“…Interestingly, expression of plakoglobin seems to be influenced by several drugs. A negative correlation was found for ASS that is known to change expression of pro- and anti-inflammatory genes 31,32 . In contrast, a positive correlation was found for ACE or AT1 antagonists.…”

Protein anabolism is key to long-term survival in high-grade serous ovarian cancer

“…Plasminogen activator inhibitor 1 (PAI-1), a component of the fibrinolytic system, inhibits apoptosis and increases tumor cell survival, representing a strong biomarker for tumor aggressiveness and poor prognosis. A mouse model of cerebral infarction demonstrated that aspirin was beneficial in thrombolysis by decreasing PAI-1 expression [ 40 ]. Therefore, use of aspirin may improve ovarian cancer prognosis by downregulating PAI-1 expression.…”

Correlations of C-Reactive Protein (CRP), Interleukin-6 (IL-6), and Insulin Resistance with Cerebral Infarction in Hypertensive Patients

“…Cerebrovascular diseases, as one of the major causes affecting human life and health at present, are one of the top 3 major fatal diseases that lead to the death in the world’s population [1]. With the aging of population and the changes of people’s life and diets in China, the morbidity, disability, and mortality rates of cerebrovascular diseases are significantly increased [2], seriously affecting the quality of life and life safety of people in China, especially the middle-aged and elderly [3].…”