| Literature DB >> 26928596 |
Lucas M Ferrer1,2, Alexandra M Monroy1,2, Jahaira Lopez-Pastrana1, Gayani Nanayakkara1, Ramon Cueto1, Ya-Feng Li1, Xinyuan Li1, Hong Wang1,3, Xiao-Feng Yang4,5, Eric T Choi6,7.
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.Entities:
Keywords: Caspase-1; Chronic kidney disease (CKD); Neointimal hyperplasia (NH); Vascular inflammation; Vascular smooth muscle cell (VSMC)
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Year: 2016 PMID： 26928596 PMCID： PMC5131710 DOI： 10.1007/s12265-016-9683-3
Source DB: PubMed Journal: J Cardiovasc Transl Res ISSN： 1937-5387 Impact factor: 4.132