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         headline:Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery
         description:To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase−/− mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase−/− mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase−/− tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.
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      headline:Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery
      description:To determine whether caspase-1 is critical in chronic kidney disease (CKD)-mediated arterial neointimal hyperplasia (NH), we utilized caspase−/− mice and induced NH in carotid artery in a CKD environment, and uremic sera-stimulated human vascular smooth muscle cells (VSMC). We made the following findings: (1) Caspase-1 inhibition corrected uremic sera-mediated downregulation of VSMC contractile markers, (2) CKD-promoted NH was attenuated in caspase−/− mice, (3) CKD-mediated downregulation of contractile markers was rescued in caspase null mice, and (4) expression of VSMC migration molecule αvβ3 integrin was reduced in caspase−/− tissues. Our results suggested that caspase-1 pathway senses CKD metabolic danger signals. Further, CKD-mediated increase of contractile markers in VSMC and increased expression of VSMC migration molecule αvβ3 integrin in NH formation were caspase-1 dependent. Therefore, caspase-1 is a novel therapeutic target for the suppression of CKD-promoted NH.
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      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
      name:Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, USA
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