title: Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery.
abstract: 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.
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.|Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
authors.forename: Lucas M
authors.initials: LM
authors.lastname: Ferrer
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.|Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Monroy
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Jahaira
authors.initials: J
authors.lastname: Lopez-Pastrana
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Gayani
authors.initials: G
authors.lastname: Nanayakkara
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Ramon
authors.initials: R
authors.lastname: Cueto
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Li
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Li
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA.|Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA. xfyang@temple.edu.|Department of Pharmacology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA. xfyang@temple.edu.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Yang
authors.affiliation: Centers for Metabolic Disease Research, Cardiovascular Research and Thrombosis Research, Lewis Katz School of Medicine, Temple University, 3500, North Broad Street, Philadelphia, PA, 19140, USA. eric.choi@tuhs.temple.edu.|Department of Surgery, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, 19140, USA. eric.choi@tuhs.temple.edu.
authors.forename: Eric T
authors.initials: ET
authors.lastname: Choi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001806:Blood Urea Nitrogen; D002340:Carotid Artery Diseases / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D017536:Carotid Artery, Common / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D020170:Caspase 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000494:pharmacology; D002465:Cell Movement; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D005838:Genotype; D006801:Humans; D006965:Hyperplasia; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D058426:Neointima; D010641:Phenotype; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics
chemical_list: D015415:Biomarkers; D061945:Caspase Inhibitors; D039302:Integrin alphaVbeta3; D020170:Caspase 1
keywords: Caspase-1; Chronic kidney disease (CKD); Neointimal hyperplasia (NH); Vascular inflammation; Vascular smooth muscle cell (VSMC)