BACKGROUND AND PURPOSE: Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis. METHODS: Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes. RESULTS: Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1β, interferon γ, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12. CONCLUSIONS: Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability.
BACKGROUND AND PURPOSE:Atherosclerosis is a progressive chronic disease, in which inflammation plays a key role. The calcium-binding proteins calgranulins including S100A8, S100A9, and S100A12 are involved in many cellular activities and pathological processes including inflammation. We therefore hypothesized that calgranulins may be markers of plaque instability in patients with carotid atherosclerosis. METHODS: Plasma levels of S100A8/A9 and S100A10 were measured in 159 consecutive patients with high-grade carotid stenosis and in 22 healthy control subjects. The mRNA levels of calgranulins were also measured within the atherosclerotic carotid plaques, and their regulation was analyzed in vitro in monocytes. RESULTS: Our main findings were: (1) plasma levels of S100A12 were significantly higher in patients with carotid atherosclerosis compared with healthy control subjects with the highest levels in patients with the most recent symptoms (ie, within 2 months); (2) plasma levels of S100A8/S100A9 showed a modest increase in patients with symptoms in the previous 2 to 6 months but not in the other patients; (3) mRNA levels of S100A8, S100A9, and S100A12 showed increased expression in atherosclerotic carotid plaques from patients with the most recent symptoms compared with the remaining patients; (4) in THP-1 monocytes, activation of Toll-like receptors 2 and 4 increased mRNA levels of S100A8, S100A9, and S10012 and interleukin-1β, interferon γ, and releasate from thrombin-activated platelets significantly enhanced the expression of S100A12. CONCLUSIONS: Our findings support a link between calgranulins and atherogenesis and suggest that these mediators, and in particular S100A12, may be related to plaque instability.
Authors: Ling Yan; Per Bjork; Radu Butuc; Joseph Gawdzik; Judy Earley; Gene Kim; Marion A Hofmann Bowman Journal: Atherosclerosis Date: 2013-02-28 Impact factor: 5.162
Authors: Enrico Ammirati; Francesco Moroni; Giuseppe Danilo Norata; Marco Magnoni; Paolo G Camici Journal: Mediators Inflamm Date: 2015-04-16 Impact factor: 4.711
Authors: Sarah R Langley; Karin Willeit; Athanasios Didangelos; Ljubica Perisic Matic; Philipp Skroblin; Javier Barallobre-Barreiro; Mariette Lengquist; Gregor Rungger; Alexander Kapustin; Ludmilla Kedenko; Chris Molenaar; Ruifang Lu; Temo Barwari; Gonca Suna; Xiaoke Yin; Bernhard Iglseder; Bernhard Paulweber; Peter Willeit; Joseph Shalhoub; Gerard Pasterkamp; Alun H Davies; Claudia Monaco; Ulf Hedin; Catherine M Shanahan; Johann Willeit; Stefan Kiechl; Manuel Mayr Journal: J Clin Invest Date: 2017-03-20 Impact factor: 14.808