@article{78b713e479be4bd6b52df86b68af4209,
title = "LIM-only protein FHL2 attenuates inflammation in vascular smooth muscle cells through inhibition of the NFκB pathway",
abstract = "Despite the advent of new-generation drug-eluting stents, in-stent restenosis remains a significant problem in patients with coronary artery disease. In- stent restenosis is defined as the gradual re-narrowing of a stented coronary artery lesion due to arterial damage with subsequent local inflammation of the vessel wall and excessive growth of the vascular smooth muscle cells (vSMCs). Four-and-a-half LIM-domain protein 2 (FHL2) is a scaffold protein involved in regulating vSMC function and inflammation. Previously we have demonstrated that FHL2 prevents vSMC proliferation in a murine carotid artery ligation model. However, the effect of FHL2 on the inflammatory response of the vSMCs is not investigated. Therefore, we studied the inflammatory response in the vessel wall of FHL2-deficient (-KO) mice after carotid artery ligation. We found that circulating cytokines and local macrophage infiltration in the ligated carotid vessels were increased in FHL2-KO mice after carotid artery ligation. Moreover, FHL2-KO vSMCs showed increased secretion of cytokines such as SDF-1α and RANTES, and enhanced activation of the NFκB pathway. Finally, we found that blocking the NFκB signalling pathway abrogated this pro-inflammatory state in FHL2-KO vSMCs. Taken together, our results demonstrate that FHL2 decreases the inflammatory response of vSMCs through inhibition of the NFkB-signalling pathway.",
keywords = "FHL2, Inflammation, NFκB pathway, Restenosis, Smooth muscle cells",
author = "{van de Pol}, V. and M. Vos and DeRuiter, {M. C.} and Goumans, {M. J.} and {de Vries}, {C. J.M.} and K. Kurakula",
note = "Funding Information: This work was supported by the Netherlands CardioVascular Research Initiative : the Dutch Heart Foundation , Dutch Federation of University Medical Centers , the Netherlands Organization for Health Research and Development , and the Royal Netherlands Academy of Sciences Grant 2012-08 and 2018-29 awarded to the Phaedra consortium ( http://www.phaedraresearch.nl ) and GENIUS consortium (CVON2011-19). This research is also supported by the Dutch Heart Foundation (BAV consortium grant 31190 ). We also acknowledge support for KK by the Dutch Lung Foundation (Longfonds) grant number- 5.2.17.198J0 and by the Leiden University Foundation grant ( W18378-2-32 ). Funding Information: This work was supported by the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation, Dutch Federation of University Medical Centers, the Netherlands Organization for Health Research and Development, and the Royal Netherlands Academy of Sciences Grant 2012-08 and 2018-29 awarded to the Phaedra consortium (http://www.phaedraresearch.nl) and GENIUS consortium (CVON2011-19). This research is also supported by the Dutch Heart Foundation (BAV consortium grant 31190). We also acknowledge support for KK by the Dutch Lung Foundation (Longfonds) grant number-5.2.17.198J0 and by the Leiden University Foundation grant (W18378-2-32). Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = feb,
day = "1",
doi = "https://doi.org/10.1016/j.vph.2019.106634",
language = "English",
volume = "125-126",
journal = "Vascular Pharmacology",
issn = "1537-1891",
publisher = "Elsevier Inc.",
}