Andreas Edsfeldt1, Helena Grufman2, Giuseppe Asciutto3, Mihaela Nitulescu2, Ana Persson4, Marie Nilsson4, Jan Nilsson2, Isabel Gonçalves4. 1. Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden. Electronic address: Andreas.Edsfeldt@med.lu.se. 2. Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden. 3. Vascular Center Malmö, Skåne University Hospital, Malmö, Sweden. 4. Experimental Cardiovascular Research Unit, Clinical Research Center, Clinical Sciences, Lund University, Sweden; Dept. of Cardiology, Skåne University Hospital, Sweden.
Abstract
AIMS: Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plasma levels of pro-inflammatory cytokines reflects inflammatory activity within atherosclerotic plaques. METHODS AND RESULTS: Cytokines were measured using Luminex immunoassay in 200 homogenized plaque extracts and plasma, obtained from 197 subjects undergoing carotid surgery. Plasma levels of macrophage inflammatory protein-1β (MIP-1β), tumor necrosis factor- α (TNF-α) and fractalkine correlated significantly, not only with plaque levels of the same cytokines but also with the abundance of several pro-inflammatory and atherogenic cytokines assessed in plaque tissue. High plasma levels (upper tertile) of MIP-1β, TNF-α and fractalkine identified the presence of a plaque with high inflammation (above median of a score based on the plaque content of MIP-1β, TNF-α, interferon-γ (IFN-γ) and fractalkine) with a sensitivity between 65 and 67% and a specificity between 78 and 83%. Furthermore, this study shows that high plasma levels of MIP-1β, TNF-α and fractalkine predict future transient ischemic attacks. CONCLUSIONS: Our findings show that the plasma levels of MIP-1β, TNF-α and fractalkine reflect the levels of several pro-atherogenic cytokines in plaque tissue and might be possible plasma markers for a vulnerable atherosclerotic disease. We thereby propose that these cytokines can be used as surrogate markers for the identification of patients with high-risk plaques.
AIMS: Inflammation is a key factor in the development of plaque rupture and acute cardiovascular events. Although imaging techniques can be used to identify vulnerable atherosclerotic plaques, we are lacking non-invasive methods, such as plasma markers of plaque inflammation that could help to identify presence of vulnerable plaques. The aim of the present study was to investigate whether increased plasma levels of pro-inflammatory cytokines reflects inflammatory activity within atherosclerotic plaques. METHODS AND RESULTS: Cytokines were measured using Luminex immunoassay in 200 homogenized plaque extracts and plasma, obtained from 197 subjects undergoing carotid surgery. Plasma levels of macrophage inflammatory protein-1β (MIP-1β), tumor necrosis factor- α (TNF-α) and fractalkine correlated significantly, not only with plaque levels of the same cytokines but also with the abundance of several pro-inflammatory and atherogenic cytokines assessed in plaque tissue. High plasma levels (upper tertile) of MIP-1β, TNF-α and fractalkine identified the presence of a plaque with high inflammation (above median of a score based on the plaque content of MIP-1β, TNF-α, interferon-γ (IFN-γ) and fractalkine) with a sensitivity between 65 and 67% and a specificity between 78 and 83%. Furthermore, this study shows that high plasma levels of MIP-1β, TNF-α and fractalkine predict future transient ischemic attacks. CONCLUSIONS: Our findings show that the plasma levels of MIP-1β, TNF-α and fractalkine reflect the levels of several pro-atherogenic cytokines in plaque tissue and might be possible plasma markers for a vulnerable atherosclerotic disease. We thereby propose that these cytokines can be used as surrogate markers for the identification of patients with high-risk plaques.
Authors: Lei Zhang; Ji Qi; Ya-Jun Jing; Bo Qin; Yi-Kai Li; Gang Liu; Xiao-Guang Guo; Shi-Jie Fu Journal: Nan Fang Yi Ke Da Xue Xue Bao Date: 2017-12-20
Authors: C Arden Pope; Aruni Bhatnagar; James P McCracken; Wesley Abplanalp; Daniel J Conklin; Timothy O'Toole Journal: Circ Res Date: 2016-10-25 Impact factor: 17.367
Authors: Shaikh M Rahman; Karalee C Baquero; Mahua Choudhury; Rachel C Janssen; Becky A de la Houssaye; Ming Sun; Shinobu Miyazaki-Anzai; Shu Wang; Naima Moustaid-Moussa; Makoto Miyazaki; Jacob E Friedman Journal: Atherosclerosis Date: 2016-04-01 Impact factor: 5.162