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Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke
Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Str. 173, Ingelheim 55216, Germany
Department of Neurology, Nordstadt Klinikum Hannover, Haltenhoffstr. 41, Hannover 30167, Germany
Institute of Biophysics, University of Hannover, Herrenhäuserstr. 2, Hannover 30419, Germany
Department of Clinical Chemistry, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover 30625, Germany
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 7 May 2012; in revised form: 21 June 2012 / Accepted: 3 July 2012 / Published: 12 July 2012
Abstract: Inflammation following ischemic brain injury is correlated with adverse outcome. Preclinical studies indicate that treatment with acetylsalicylic acid + extended-release dipyridamole (ASA + ER-DP) has anti-inflammatory and thereby neuroprotective effects by inhibition of monocyte chemotactic protein-1 (MCP-1) expression. We hypothesized that early treatment with ASA + ER-DP will reduce levels of MCP-1 also in patients with ischemic stroke. The EARLY trial randomized patients with ischemic stroke or TIA to either ASA + ER-DP treatment or ASA monotherapy within 24 h following the event. After 7 days, all patients were treated for up to 90 days with ASA + ER-DP. MCP-1 was determined from blood samples taken from 425 patients on admission and day 8. The change in MCP-1 from admission to day 8 did not differ between patients treated with ASA + ER-DP and ASA monotherapy (p > 0.05). Comparisons within MCP-1 baseline quartiles indicated that patients in the highest quartile (>217–973 pg/mL) showed improved outcome at 90 days if treated with ASA + ER-DP in comparison to treatment with ASA alone (p = 0.004). Our data does not provide any evidence that treatment with ASA + ER-DP lowers MCP-1 in acute stroke patients. However, MCP-1 may be a useful biomarker for deciding on early stroke therapy, as patients with high MCP-1 at baseline appear to benefit from early treatment with ASA + ER-DP.
Keywords: ischemic stroke; monocyte chemoattractant protein-1 (MCP-1); antithrombotic therapy; neuroprotection; dipyridamole; acetylsalicylic acid (ASA)
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Worthmann, H.; Dengler, R.; Schumacher, H.; Schwartz, A.; Eisert, W.G.; Lichtinghagen, R.; Weissenborn, K. Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke. Int. J. Mol. Sci. 2012, 13, 8670-8678.
Worthmann H, Dengler R, Schumacher H, Schwartz A, Eisert WG, Lichtinghagen R, Weissenborn K. Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke. International Journal of Molecular Sciences. 2012; 13(7):8670-8678.
Worthmann, Hans; Dengler, Reinhard; Schumacher, Helmut; Schwartz, Andreas; Eisert, Wolfgang G.; Lichtinghagen, Ralf; Weissenborn, Karin. 2012. "Monocyte Chemotactic Protein-1 as a Potential Biomarker for Early Anti-Thrombotic Therapy after Ischemic Stroke." Int. J. Mol. Sci. 13, no. 7: 8670-8678.