High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction

Elmas, Elif; Lang, Siegfried; Dempfle, Carl Erik; Kälsch, Thorsten; Hannak, Dieter; Sueselbeck, Tim; Wolpert, Christian; Borggrefe, Martin; Brueckmann, Martina

doi:10.1515/cclm.2007.286

Cited by 28 publications

(22 citation statements)

References 38 publications

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“…IL-8 is a key proinflammatory mediator that has been shown to be elevated in patients with ventricular fibrillation complicating myocardial infarction [29]. As inflammation does not play a role in the pathogenesis of HCM, IL-8 plasma levels were not significantly correlated with the extent of LGE.…”

Section: Discussionmentioning

confidence: 97%

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Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Elmas

Doesch

Fluechter

et al. 2010

Int J Cardiovasc Imaging

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We aimed to determine the diagnostic performance of biomarkers in predicting myocardial fibrosis assessed by late gadolinium enhancement (LGE) cardiovascular magnetic resonance imaging (CMR) in patients with hypertrophic cardiomyopathy (HCM). LGE CMR was performed in 40 consecutive patients with HCM. Left and right ventricular parameters, as well as the extent of LGE were determined and correlated to the plasma levels of midregional pro-atrial natriuretic peptide (MR-proANP), midregional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), carboxy-terminal pro-vasopressin (CT-proAVP), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8). Myocardial fibrosis was assumed positive, if CMR indicated LGE. LGE was present in 26 of 40 patients with HCM (65%) with variable extent (mean: 14%, range: 1.3-42%). The extent of LGE was positively associated with MR-proANP (r = 0.4; P = 0.01). No correlations were found between LGE and MR-proADM (r = 0.1; P = 0.5), CT-proET-1 (r = 0.07; P = 0.66), CT-proAVP (r = 0.16; P = 0.3), MMP-9 (r = 0.01; P = 0.9), TIMP-1 (r = 0.02; P = 0.85), and IL-8 (r = 0.02; P = 0.89). After adjustment for confounding factors, MR-proANP was the only independent predictor associated with the presence of LGE (P = 0.007) in multivariate analysis. The area under the ROC curve (AUC) indicated good predictive performance (AUC = 0.882) of MR-proANP with respect to LGE. The odds ratio was 1.268 (95% confidence interval 1.066-1.508). The sensitivity of MR-proANP at a cut-off value of 207 pmol/L was 69%, the specificity 94%, the positive predictive value 90% and the negative predictive value 80%. The results imply that MR-proANP serves as a novel marker of myocardial fibrosis assessed by LGE CMR in patients with HCM.

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Section: Discussionmentioning

confidence: 97%

“…Markers of inflammation and plaque stabilization were measured by ELISA [29]. IL-8, MMP-9 and TIMP-1 concentrations were measured with commercially available assays from Amersham Pharmacia (Braunschweig, Germany; product codes RPN 2611 for TIMP-1, RPN 2614 for MMP-9 and RPN 2764 for IL-8).…”

Section: Ct-proavpmentioning

confidence: 99%

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Elmas

Doesch

Fluechter

et al. 2010

Int J Cardiovasc Imaging

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“…12) Several reports have provided evidence to support the concept that increased MMP activity may contribute to the development of LV remodeling and a poor prognosis. 11,[13][14][15][16][17][18][19][20] Coexpression of MMP and TIMP has been shown in the myocardium. However, whether this is reflected by increased activity of the endogenous inhibitor system TIMP-1 in the serum and to what degree MMP inhibition may influence the LV remodeling process is currently under investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, there is evidence about the influence of cytokines like TNF and IL-1 on TIMP and MMP activation and activity after acute myocardial infarction. [38][39][40] Conclusion: Increased serum levels of TIMP-1 can be detected within 12 hours in patients with a first acute myocardial infarction, suggesting an early onset of myocardial remodeling. We hypothesised that in the early phase of myocardial infarction, this may reflect the ability to prevent a high turnover rate of ECM caused by MMP activation which has been reported to occur with the development of chronic heart failure.…”

Section: Discussionmentioning

confidence: 99%

Increased Serum Levels of Tissue Inhibitor of Metalloproteinase-1 in Patients With Acute Myocardial Infarction

Dinh

Füth

Scheffold³

et al. 2009

Int. Heart J.

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SummaryIt has been suggested that matrix-metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs) play a major role in the regulation of myocardial remodeling. Myocardial extracellular matrix (ECM) is highly susceptible to ischemic injury in acute myocardial infarction (AMI).We measured serum levels of TIMP-1 in the early hours of AMI to study the kinetics of these enzymes in an early ischemic phase.TIMP-1 was measured in 25 patients with AMI and 116 healthy controls. Blood samples were obtained during the first 12 hours after hospital admission. Left ventricular function (LVF) and hemodynamic data were collected during coronary intervention.TIMP-1 was significantly elevated in patients with AMI within the first hours compared to controls (P < 0.05). No significant difference was observed between patients with preserved LVF and with impaired LVF. Elevated TIMP-1 levels did not correlate with increased levels of CK or CK-MB band during the first hours after AMI.Increased TIMP-1 can be detected within 12 hours in patients with AMI, suggesting early onset of remodeling. Elevation of TIMP-1 may be a surrogate marker for increased ECM-turnover. The prognostic relevance needs to be proved in long-term studies. (Int Heart J 2009; 50: 421-431)

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“…In the complex inflammatory milieu surrounding acute LAD occlusion, other cytokines such as hepatocyte growth factor (Yumoto 2005), interleukin-8 (IL-8), metalloproteinase-1 (TIMP-1) (Elmas 2007), or activation of the phosphatidylinositol-3 kinase pathway (Takahama 2006), may have a more causal effect on development of VF in AMI. A lessened role of endothelin in the pathogenesis of VF may account for the disparate results of endothelin receptor blockade in the literature.…”

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confidence: 99%

Endothelin-1 Is Not Predictive of Ventricular Ectopy or Ventricular Fibrillation during Acute Myocardial Ischemia

Shah

Niemann²,

Youngquist³

et al. 2008

Journal of Interferon & Cytokine Research

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Background Endothelin(ET)-1 (ET-1) increases after myocardial infarction and may have effects on myocardial function. ET-1 has also been shown to affect the action potential (AP) which may be arrhythmogenic and predispose to ventricular fibrillation (VF). The effects of endothelin-2 (ET-2) and endothelin-3 (ET-3) are uncertain. We hypothesized that the endothelins increase during acute ischemia and that plasma levels are predictive of ischemically induced VF. Methods Thirty-four domestic swine underwent balloon occlusion of the proximal LAD coronary artery. Occlusion was confirmed angiographically. Venous samples were collected from the right atrium at baseline and at 5 minutes intervals for 30 minutes or until VF induction. ET-1, ET-2, and ET-3 were measured using ELISA. Changes in plasma concentrations were assessed using repeated measures ANOVA with Dunnett’s. A p-value of <0.05 was considered statistically significant. Results All animals had angiographic evidence of successful proximal LAD occlusion. ET-1 levels were significantly increased from a baseline at 20 min and remained elevated during 30 min of occlusion. ET-2 and ET-3 levels did not change from baseline values (figure, mean ± SE). VF occurred in 60% of animals. Peak ET-1 values were not significantly different between VF and non-VF animals (6.2 ± 2.2 vs. 4.8 ± 2.3 pg/ml). No single ET-1 value had a VF predictive value >50%. Conclusions There is a significant increase in ET-1 level within 20 min of acute myocardial ischemia. Despite known effects of ET-1 on the AP, this increase did not correlate with the occurrence of VF.

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High plasma levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and interleukin-8 (IL-8) characterize patients prone to ventricular fibrillation complicating myocardial infarction

Cited by 28 publications

References 38 publications

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Midregional pro-atrial natriuretic peptide: a novel marker of myocardial fibrosis in patients with hypertrophic cardiomyopathy

Increased Serum Levels of Tissue Inhibitor of Metalloproteinase-1 in Patients With Acute Myocardial Infarction

Endothelin-1 Is Not Predictive of Ventricular Ectopy or Ventricular Fibrillation during Acute Myocardial Ischemia

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