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 - 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)
UR - http://www.scopus.com/inward/record.url?scp=84959375857&partnerID=8YFLogxK
U2 - 10.1007/s12265-016-9683-3
DO - 10.1007/s12265-016-9683-3
M3 - Article
C2 - 26928596
AN - SCOPUS:84959375857
SN - 1937-5387
VL - 9
SP - 135
EP - 144
JO - Journal of Cardiovascular Translational Research
JF - Journal of Cardiovascular Translational Research
IS - 2
ER -