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Background: Soluble ST2 (sST2), a member of the IL-1 receptor family, has been proposed as a novel biomarker with predictive value for heart failure and mortality in patients suffering from cardiovascular diseases. The influence of clinical characteristics on variability of sST2 levels is relatively unexplored. Here, we studied the effect of cardiovascular interventions and clinical characteristics on plasma sST2 expression levels., Material and Methods: In the current study, sST2 levels were assessed in the plasma of patients scheduled for coronary artery bypass grafting (CABG) (n = 76), percutaneous coronary intervention (PCI) (n = 68) or peripheral vascular surgery (n = 27)., Results: Age was the only classical risk factor significantly correlating with sST2 levels. Soluble ST2 levels were significantly increased 1 h after CABG (48 [33-70] vs. 61 [42-89] pg/mL, P = 0·001) and increased even further after 24 h (1116 [578-13 666] pg/mL, P < 0·001). An average threefold increase in sST2 levels was also observed in patients 24 h after peripheral interventions (30 [21-41] vs. 98 [48-211] pg/mL, P < 0·001). Two months after PCI, we found that sST2 levels were significantly higher compared with baseline levels (41 [29-61] vs. 48 [31-80] pg/mL, P = 0·007, n = 52). In addition, we did not observe an association between sST2 and any inflammatory or cardiac-specific markers that were measured in this study., Conclusions: Soluble ST2 increases significantly following cardiovascular interventions. The notion of a recent cardiovascular intervention is a strong determinant of sST2 levels and therefore needs to be taken into account when exploring sST2 as predictor of future cardiovascular events., (© 2012 The Authors. European Journal of Clinical Investigation © 2012 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: We tested the hypothesis that high TGF-β1 content in atherosclerotic plaques and high TGF-β1 serum levels are associated with lower risk of coronary events in two independent prospective studies., Materials and Methods: In the prospective Athero-Express biobank study, total TGF-β1 plaque levels were measured in 632 atherosclerotic lesions from patients who underwent carotid endarterectomy. In a population-based case-cohort study within the Monitoring of trends and determinants in cardiovascular disease (MONICA)/Cooperative Health Research in the Region of Augsburg (KORA) Augsburg studies, baseline total TGF-β1 serum levels were measured in 333 individuals with and 1728 without incident coronary events., Results: Patients with TGF-β1 content in their plaques above the study median did not have a lower risk of coronary events than patients with lower TGF-β1 levels [adjusted HR (95% CI) 1·46 (0·83-2·53); P = 0·16; mean follow-up 2·6 ± 0·7 years] in the Athero-Express biobank study. Cox proportional hazard models adjusting for age, sex, body mass index, metabolic factors, lifestyle factors and survey did not reveal a significant association between TGF-β1 serum levels and incident coronary events [HR (95% CI) for increasing TGF-β1 tertiles 1·0, 1·22 (0·88-1·68), 1·13 (0·82-1·57); P = 0·47; mean follow-up: 10·8 ± 4·6 years] in the MONICA/KORA Augsburg studies., Conclusion: Our results indicate that high TGF-β1 content in human atherosclerotic plaques and high serum levels of TGF-β1 are not associated with reduced risk of coronary events., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Background: Hyaluronic acid is expressed in atherosclerotic lesions, but its exact role in atherosclerotic disease remains unknown. As degradation of hyaluronic acid by hyaluronidase into low molecular weight hyaluronic acid (LMW-HA) is associated with inflammation and Matrix Metalloproteinase (MMP)-9 activity, we hypothesized that hyaluronic acid metabolism is increased in plaques with unstable characteristics like large lipid core, high number of macrophages, MMP-9 activity, low collagen and smooth muscle cell content., Materials and Methods: Protein was isolated from 68 carotid artery specimens. The adjacent plaque segment was characterized for the histological parameters: lipid core, macrophage, collagen, smooth muscle cell (SMC) content and the amount of intra-plaque thrombus. Hyaluronidase activity, total hyaluronic acid and LMW-HA expression, the standard hayaluronic acid receptor CD44s and the VEGF-A binding isoform CD44v3, MMP-9 activity and the plaque instability associated growth factor Vascular Endothial Growth Factor (VEGF)-A were analysed and correlated with histological characteristics., Results: Hyaluronidase activity, LMW-HA and CD44 expression (CD44s, CD44v3) levels were increased in atheromatous plaques compared with fibrous plaques. Total hyaluronic acid did not correlate with plaque instability. MMP-9 activity correlated with CD44s, hyaluronidase and LMW-HA expression. CD44v3 correlated with the angiogenic factor VEGF-A. In vitro stimulation of macrophages with LMW-HA increased MMP-9 activity., Conclusions: We show for the first time that increased hyaluronic acid metabolism and elevated CD44 levels are associated with plaque destabilization potentially by increased MMP-9 activity and stimulation of angiogenesis.

The family of Toll-like receptors (TLRs) initiates an innate immune response after recognition of pathogen-associated molecular patterns (PAMPs). Evidence is accumulating that TLRs, and particularly TLR4, are important players in the initiation and progression of atherosclerotic disease. Not only exogenous ligands but also endogenous ligands that are expressed during arterial injury are recognized by TLR4. Mouse knockout studies and epidemiological studies of human TLR4 polymorphisms have demonstrated that the TLR4 might play a role in the initiation and progression of atherosclerosis. This review will summarize the latest progression in research on the role of TLR4 in arterial occlusive disease In addition, the potential of intervention in TLR4 signalling to influence progression of atherosclerotic disease is discussed.

Haptoglobin is an acute phase protein known to be highly expressed in the liver. Recently, we showed increased local arterial haptoglobin expression after flow-induced arterial remodelling and found that haptoglobin is involved in cell migration and arterial restructuring probably through accumulation of a temporary gelatin matrix. Since cell migration and matrix turnover are important features in the pathology of arthritis and cancer, we hypothesized that haptoglobin is also locally expressed in arthritic and oncological tissues. In this study, we investigated local haptoglobin expression in arthritic rats (n = 12) using semi-quantitative PCR and Western blotting, and we studied haptoglobin mRNA localization in human kidney tumours (n = 3) using in situ hybridization. The arthritic rats demonstrated an increase of haptoglobin mRNA (2.5-fold, P < 0.001) and protein (2.6-fold, P < 0.001) in the arthritic Achilles tendon. Haptoglobin protein was also increased in the arthritic ankle (2.6-fold, P < 0.001) but not in the non-arthritic knee. In human kidney tumours, tumour and stromal cells produced haptoglobin mRNA. This study shows that the liver protein haptoglobin is, in addition to the artery, also expressed in arthritic and oncological tissues that are recognized for enhanced cell migration and matrix turnover.