OBJECTIVES: Based on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization. METHODS: The study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets). RESULTS: Our main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease. (ii) CXCL13 showed increased expression within atherosclerotic carotid plaques as compared with non-atherosclerotic vessels. (iii) Within the atherosclerotic lesions, CXCR5 and CXCL13 were expressed by macrophages and SMC in all stages of plaque progression. (iv) Releasate from activated platelets and toll-like receptor activation enhanced the expression of CXCL13 in THP-1 monocytes and primary monocytes. (v) In vitro, CXCL13 exerted anti-apoptotic effects in primary monocytes, THP-1 macrophages, and vascular SMC. (vi) CXCL13 increased arginase-1, transforming growth factor-β, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques. CONCLUSION: Levels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction.
OBJECTIVES: Based on the newly recognized role of the homeostatic chemokines in inflammation, we hypothesized that CXCL13 could modulate atherogenesis and plaque destabilization. METHODS: The study included in vivo analyses in patients with carotid atherosclerosis and in vitro experiments in cells involved in atherogenesis (ie, monocytes/macrophages, vascular smooth muscle cells [SMC], and platelets). RESULTS: Our main findings were: (i) Patients with carotid atherosclerosis (n = 130) had increased plasma levels of CXCL13 with particularly high levels in symptomatic disease. (ii) CXCL13 showed increased expression within atherosclerotic carotid plaques as compared with non-atherosclerotic vessels. (iii) Within the atherosclerotic lesions, CXCR5 and CXCL13 were expressed by macrophages and SMC in all stages of plaque progression. (iv) Releasate from activated platelets and toll-like receptor activation enhanced the expression of CXCL13 in THP-1 monocytes and primary monocytes. (v) In vitro, CXCL13 exerted anti-apoptotic effects in primary monocytes, THP-1 macrophages, and vascular SMC. (vi) CXCL13 increased arginase-1, transforming growth factor-β, and interleukin-10 expression in THP-1 cells and in samples from isolated carotid plaques. CONCLUSION: Levels of CXCL13 are increased in carotid atherosclerosis both systemically and within the atherosclerotic lesion. Based on our in vitro findings, we hypothesize a potential plaque stabilizing effects of CXCL13-CXCR5 interaction.
Authors: Chiara Giannarelli; David T Rodriguez; M Urooj Zafar; Daniel Christoffel; Vincent Vialou; Catherine Peña; Ana Badimon; Georgia F Hodes; Pauline Mury; Jacklyn Rabkin; Matilde Alique; Giulia Villa; Carmen Argmann; Eric J Nestler; Scott J Russo; Juan J Badimon Journal: Thromb Haemost Date: 2017-01-12 Impact factor: 5.249
Authors: Yanina R Timasheva; Timur R Nasibullin; Ilsiyar A Tuktarova; Vera V Erdman; Olga E Mustafina Journal: Mol Biol Rep Date: 2018-07-17 Impact factor: 2.316
Authors: R A van Dijk; A J F Duinisveld; A F Schaapherder; A Mulder-Stapel; J F Hamming; J Kuiper; O J de Boer; A C van der Wal; F D Kolodgie; R Virmani; J H N Lindeman Journal: J Am Heart Assoc Date: 2015-03-26 Impact factor: 5.501
Authors: Sylwia Wasiak; Dean Gilham; Laura M Tsujikawa; Christopher Halliday; Karen Norek; Reena G Patel; Kevin G McLure; Peter R Young; Allan Gordon; Ewelina Kulikowski; Jan Johansson; Michael Sweeney; Norman C Wong Journal: Data Brief Date: 2016-07-29