TY - JOUR
T1 - Caspase-1 Plays a Critical Role in Accelerating Chronic Kidney Disease-Promoted Neointimal Hyperplasia in the Carotid Artery
AU - Ferrer, Lucas M.
AU - Monroy, Alexandra M.
AU - Lopez-Pastrana, Jahaira
AU - Nanayakkara, Gayani
AU - Cueto, Ramon
AU - Li, Ya feng
AU - Li, Xinyuan
AU - Wang, Hong
AU - Yang, Xiao feng
AU - Choi, Eric T.
N1 - Funding Information:
This work was supported by Temple University’s fund to ETC., the American Heart Association Postdoctoral Fellowship to YFL, and the National Institutes of Health Grants to ETC., XFY, and HW.
Funding Information:
This work was supported by Temple University's fund to ETC., the American Heart Association Postdoctoral Fellowship to YFL, and the National Institutes of Health Grants to ETC., XFY, and HW.
Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2016/4/1
Y1 - 2016/4/1
N2 - 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.
AB - 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.
KW - Caspase-1
KW - Chronic kidney disease (CKD)
KW - Neointimal hyperplasia (NH)
KW - Vascular inflammation
KW - Vascular smooth muscle cell (VSMC)
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U2 - 10.1007/s12265-016-9683-3
DO - 10.1007/s12265-016-9683-3
M3 - Article
C2 - 26928596
AN - SCOPUS:84959375857
VL - 9
SP - 135
EP - 144
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
SN - 1937-5387
IS - 2
ER -