CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Eduard Shantsila, MD and
Gregory Y.H. Lip, MD*
* Haemostasis Thrombosis and Vascular Biology Unit, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham B18 7QH, England, United Kingdom (Email: g.y.h.lip{at}bham.ac.uk).
We thank Drs. Kavsak and Jaffe for their discussion regarding the paper by Tsujioka et al. (1) and our accompanying editorial (2), and we agree that the role of monocytes in the pathogenesis of acute coronary syndromes (ACS) includes a lot of undiscovered areas. Although the significance of high monocyte count for the development of atherothrombotic events and unfavorable course of the recovery from them has been uniformly demonstrated, some controversy still exists in relation to the precise mechanisms responsible for monocyte recruitment to the damaged myocardium in general and monocyte chemoattractant protein (MCP)-1 in particular (3,4).
In addition to a small study by Matsumori et al. (5), other experimental and clinical studies support significant up-regulation of MCP-1 in ACS (as recently reviewed) (6). In the largest of such studies, the OPUS–TIMI (Orbofiban in Patients with Unstable coronary Syndromes–Thrombolysis In Myocardial Infarction) 16 trial (5), MCP-1 was significantly increased in 2,270 patients with ACS compared with stable subjects and was an independent prognostic factor for adverse outcomes (7).
Although the study by Kavsak et al. (8) on 216 patients with ACS did not reveal significant dynamics in MCP-1 at early stages of ACS, this work was limited by only 2 time-points included in the analysis (i.e., admission within 6 h after the onset of symptoms, and at 3 to 12 h later [median 6.5 h]), whereas monocytes are known to peak at 48 to 72 h after ACS onset. Additionally, the study did not include a stable control group and thus might not provide the basis to challenge the hypothesis that "prompt up-regulation of CCR-2 expressing CD14+CD16- monocytes" (2).
In fact, a critical role of MCP-1 for mobilization of monocytes from bone marrow and their homing to the sites of damage has been repeatedly shown. In contrast, mechanisms of recruitment of CD16+ monocyte population are less established. These cells can differentiate from CD16- monocytes or might be formed directly in bone marrow (9). Indeed, their biological role in human cardiac pathology is only scarcely analyzed. The many observations reported by Tsujioka et al. (1) (e.g., reduction of CD16+ monocytes in ACS patients at admission) do not have a robust explanation at present, thus raising further questions for future research. We agree with Drs. Kavsak and Jaffe that "data in a more diverse group" of ACS patients on the dynamics of monocyte subsets are needed to shed further light on their clinical implications.
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References
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1. Tsujioka H, Imanishi T, Ikejima H, et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction J Am Coll Cardiol 2009;54:130-138.[Abstract/Free Full Text]2. Shantsila E, Lip GYH. Monocyte diversity in myocardial infarction J Am Coll Cardiol 2009;54:139-142.[Free Full Text] 3. Horne BD, Anderson JL, John JM, et al. Which white blood cell subtypes predict increased cardiovascular risk? J Am Coll Cardiol 2005;45:1638-1643.[Abstract/Free Full Text] 4. Maekawa Y, Anzai T, Yoshikawa T, et al. Prognostic significance of peripheral monocytosis after eperfused acute myocardial infarction: a possible role for left ventricular remodeling J Am Coll Cardiol 2002;39:241-246.[Abstract/Free Full Text] 5. Matsumori A, Furukawa Y, Hashimoto T, et al. Plasma levels of the monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 are elevated in patients with acute myocardial infarction J Mol Cell Cardiol 1997;29:419-423.[CrossRef][Web of Science][Medline] 6. Shantsila E, Lip GY. Monocytes in acute coronary syndromes Arterioscler Thromb Vasc Biol 2009;29:1433-1438.[Abstract/Free Full Text] 7. de Lemos JA, Morrow DA, Sabatine MS, et al. Association between plasma levels of monocyte chemoattractant protein-1 and long-term clinical outcomes in patients with acute coronary syndromes Circulation 2003;107:690-695.[Abstract/Free Full Text] 8. Kavsak PA, Ko DT, Newman AM, et al. Risk stratification for heart failure and death in an acute coronary syndrome population using inflammatory cytokines and N-terminal pro-brain natriuretic peptide Clin Chem 2007;53:2112-2118.[Abstract/Free Full Text] 9. Serbina NV, Jia T, Hohl TM, Pamer EG. Monocyte-mediated defense against microbial pathogens Annu Rev Immunol 2008;26:421-452.[CrossRef][Web of Science][Medline]
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