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• Oxidized low density lipoprotein induced caspase-1 mediated pyroptotic cell death in macrophages: implication in lesion instability?

Schema {🗺️}

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         headline:MLKL Aggravates Ox-LDL-Induced Cell Pyroptosis via Activation of NLRP3 Inflammasome in Human Umbilical Vein Endothelial Cells
         description:Atherosclerosis is a progressive chronic inflammation in the arterial walls. It is believed that the deposition of low-density lipoprotein (LDL) and its damage to endothelial cells play a vital role in atherosclerosis. Oxidized LDL (Ox-LDL) was confirmed to induce endothelial cell pyroptosis which plays an important role in intima inflammation and the development of atherosclerosis, but the underlying molecular mechanism needs to be explored. Here, we showed that ox-LDL upregulated the expression of mixed lineage kinase domain-like (MLKL) protein at both the mRNA and protein levels in endothelial cells, associated with the augment of pro-caspase-1 cleavage, interleukin-1β (IL-1β) maturation, pro-IL-1β production, and lactate dehydrogenase (LDH) release. Overexpression of MLKL substantially aggravated ox-LDL-induced increasing levels of caspase-1, IL-1β, pro-IL-1β, and LDH. MLKL-induced caspase-1 activation and IL-1β maturation were abolished by NLR family, pyrin domain-containing 3 (NLRP3) specific inhibitor MCC950, or extracellular high potassium concentration. Our findings indicated that MLKL is essential for regulation of ox-LDL-induced pyroptosis and inflammation through the activation of NLRP3 inflammasome, and suggested that MLKL could act as potential therapeutic targets to ameliorate atherosclerosis-related diseases.
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            address:
               name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      name:Yan-Wei Hu
      url:http://orcid.org/0000-0002-1601-412X
      affiliation:
            name:Southern Medical University
            address:
               name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
            name:Guangzhou Medical University
            address:
               name:Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Qian Wang
      affiliation:
            name:Southern Medical University
            address:
               name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
            name:Southern Medical University
            address:
               name:Laboratory Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Clinical Laboratory, Guangzhou Twelfth People’s Hospital, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Department of Clinical Laboratory, Guangzhou Women & Children Medical Center, Guangzhou Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
      name:Laboratory Medicine Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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