{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:52:29Z","timestamp":1787017949523,"version":"build-2736575974"},"reference-count":54,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cerebrovasc Dis"],"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; This study aimed to elucidate the mechanisms underlying endothelial injury in the context of intracranial aneurysm formation and development, which are associated with vascular endothelial injury caused by hemodynamic abnormalities. Specifically, we focus on the involvement of PKC\u03b1, an intracellular signaling transmitter closely linked to vascular diseases, and its role in activating MAPK. Additionally, we investigate the protective effects of PPAR\u03b3, a vasculoprotective factor known to attenuate vascular injury by mitigating the inflammatory response in the vessel wall. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; The study employs a modified T-chamber to replicate fluid flow conditions at the artery bifurcation, allowing us to assess wall shear stress effects on human umbilical vein endothelial cells in vitro. Through experimental manipulations involving PKC\u03b1 knockdown and Ca&lt;sup&gt;2+&lt;\/sup&gt; and MAPK inhibitors, we evaluated the phosphorylation status of PKC\u03b1, NF-\u03baB, ERK5, ERK1\/2, JNK1\/2\/3, and P38, as well as the expression levels of PPAR\u03b3, NF-\u03baB, and MMP2 via Western blot analysis. The cellular localization of phosphorylated NF-\u03baB was determined using immunofluorescence. &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; Our results showed that impinging flow resulted in the activation of PKC\u03b1, followed by the phosphorylation of ERK5, ERK1\/2, and JNK1\/2\/3, leading to a decrease in PPAR\u03b3 expression, an increase in the expression of NF-\u03baB and MMP2, and the induction of apoptotic injury. Inhibition of PKC\u03b1 activation or knockdown of PKC\u03b1 using shRNA leads to a suppression of ERK5, ERK1\/2, JNK1\/2\/3, and P38 phosphorylation, an elevation in PPAR\u03b3 expression, and a reduction in NF-\u03baB and MMP2 expression, alleviated apoptotic injury. Furthermore, we observe that the regulation of PPAR\u03b3, NF-\u03baB, and MMP2 expression is influenced by ERK5 and ERK1\/2 phosphorylation, and activation of PPAR\u03b3 effectively counteracts the elevated expression of NF-\u03baB and MMP2. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; Our findings suggest that the PKC\u03b1\/ERK\/PPAR\u03b3 pathway plays a crucial role in mediating endothelial injury under conditions of impinging flow, with potential implications for vascular diseases and intracranial aneurysm development.<\/jats:p>","DOI":"10.1159\/000539000","type":"journal-article","created":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T17:00:31Z","timestamp":1714496431000},"page":"1-13","source":"Crossref","is-referenced-by-count":3,"title":["Impinging Flow Mediates Vascular Endothelial Cell Injury through the PKC\u03b1\/ERK\/PPAR\u03b3 Pathway in 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