HMGB1 Is Associated with Atherosclerotic Plaque Composition and Burden in Patients with Stable Coronary Artery Disease

Abstract

ObjectivesThe role of inflammation in atherosclerosis is widely appreciated. High mobility group box 1 (HMGB1), an injury-associated molecular pattern molecule acting as a mediator of inflammation, has recently been implicated in the development of atherosclerosis. In this study, we sought to investigate the association of plasma HMGB1 with coronary plaque composition in patients with suspected or known coronary artery disease (CAD).DesignHMGB1, high sensitive troponin T (hsTnT) and high sensitive C-reactive protein (hsCRP) were determined in 152 consecutive patients with suspected or known stable CAD who underwent clinically indicated 256-slice coronary computed tomography angiography (CCTA). Using CCTA, we assessed 1) coronary calcification, 2) non-calcified plaque burden and 3) the presence of vascular remodeling in areas of non-calcified plaques.ResultsUsing univariate analysis, hsCRP, hsTnT and HMGB1 as well as age, and atherogenic risk factors were associated with non-calcified plaque burden (r = 0.21, p = 0.009; r = 0.48, p<0.001 and r = 0.34, p<0.001, respectively). By multivariate analysis, hsTnT and HMGB1 remained independent predictors of the non-calcified plaque burden (r = 0.48, p<0.01 and r = 0.34, p<0.001, respectively), whereas a non-significant trend was noticed for hs-CRP (r = 0.21, p = 0.07). By combining hsTnT and HMGB1, a high positive predictive value for the presence of non-calcified and remodeled plaque (96% and 77%, respectively) was noted in patients within the upper tertiles for both biomarkers, which surpassed the positive predictive value of each marker separately.ConclusionsIn addition to hs-TnT, a well-established cardiovascular risk marker, HMGB1 is independently associated with non-calcified plaque burden in patients with stable CAD, while the predictive value of hs-CRP is lower. Complementary value was observed for hs-TnT and HMGB1 for the prediction of complex coronary plaque.

Glycyrrhizin, a High-Mobility Group Box 1 Inhibitor, Improves Lipid Metabolism and Suppresses Vascular Inflammation in Apolipoprotein E Knockout Mice

“…HMGB1 also interacts with the receptor for advanced glycation end products or multiple TLRs and thus plays a role in inducing the release of cytokines, such as tumor necrosis factor (TNF)-a, IL-6, IL-1, and IL-8, to stimulate innate immunity. Meanwhile, Andrassy et al [18] showed that HMGB1 is related to the severity of coronary artery stenosis. These findings suggest that the release of HMGB1 plays an important role in promoting inflammation and atherogenesis.…”

Assessment of coronary artery disease using coronary computed tomography angiography and biochemical markers

“…Only weak association was detected for hsCRP Blaha et al [68] hsCRP 4-sl. MDCT 6762 hsCRP was not associated with coronary artery calcification Duivenvoorden et al [70] hsCRP, MPO, and others 18 FDG-PET/CT 130 MPO levels are associated with carotid plaque inflammation Andrassy et al [62] HMBG-1 256-sl. MDCT 152 HMBG1 is associated with the composition and extend of atherosclerotic plaques Nakazato et al [64] LDL, HDL, TC ≥ 64-sl.…”

“…In an experimental setting, high mobility group box 1 (HMBG1) protein was found to be a critical mediator of acute ischemic injury, predicting adverse outcomes after myocardial infarction [60,61] . In addition, we could show that HMBG1 serum levels are associated with coronary calcification and with non-calcified plaque composition in patients with suspected or known stable CAD [62] . Incorporation of ox-LDL transforms macrophages into foam cells, which built the core of atherosclerotic plaques.…”

Critical role of RAGE and HMGB1 in inflammatory heart disease

“…The hs-TnT was measured by the electrochemiluminescence method (ECLIA; Elecsys 2010 analyzer). Details of the test principle have been described before (54). For a quantitative determination of HMGB1 protein in serum/plasma, a highsensitivity sandwich ELISA (Shino-Test) was performed according to the manufacturer's instructions (55).…”