No doubt that in a number of situations where human beings are involved it is often a matter of heart. And when it comes to acute coronary syndromes (ACS), the assumption is quite appropriate. ACS, including unstable angina (absence of heart muscle damage) and several forms of myocardial infarction (heart muscle damage), have been extensively linked to the presence and activity of a family of compounds called chemokines. Recently, a team of EVGN scientists led by Erik A.L. Biessen – formerly working at the division of Biopharmaceutics (Leiden University) and presently at the Department of Pathology, CARIM, Academic University Hospital Maastricht, The Netherlands - identified one such chemokine whose levels are unusually high during the acute phase of cardiac pathologies. Their investigation, published in the Journal of Molecular and Cellular Cardiology, is shedding light on these syndromes as a whole, paving the way towards early detection of dangerous symptoms and, possibly, curative treatments.

For a long time, Acute Myocardial Infarction (AMI) was confirmed by clinicians after positive detection of myocardial enzymes in the serum of patients. These indicators, however, were far from being precise and an acute episode could sometimes be masked by other kinds of injuries or pathologies, if not go unnoticed. Recent investigations revealed that a family of compounds called chemokines display a better degree of trustworthiness at the moment of diagnosis.

“Chemokines – explains Saskia C.A. de Jager, from the Division of Biopharmaceutics, Leiden Amsterdam Center for Drug research (Leiden University) and first author of the study – are considered pivotal in a number of noxious events that afflict the cardiac muscle. They promote plaque erosion and rupture, recruit and activate leukocyte towards the site of injury – an event that starts hours after a stroke - and are responsible for myocardial injury after ischemia, because they are likely to promote deranged remodelling. Besides, enhanced coagulability has been often associated to the presence and activity of certain chemokines. Not all of them, however, have been clearly identified in association with AMI. For this reason, we started this investigation with the aim of drawing a clearer picture of their profile in people with acute coronary syndromes”.

A group of 44 patients with Acute Myocardial Infarction and 22 control subjects were examined by the team, that collected samples of their blood for a thorough analysis. Circulating chemokine levels were assessed using a sophisticated and sensitive method, and a complete profile was eventually traced. “After determining the individual levels of the most common circulating chemokines – says de Jager – we found that three of them - CCL3, CCL5 and CXCL8 - were prevalent. In particular, CCL3’s concentration was higher than normal in patients with AMI, counterparted by lower than usual levels of another chemokine (CXCL10). CCL3 was up-regulated also in people with unstable angina pectoris, a condition of chest pain revealing that the heart is suffering because of lack of oxygen. Predictably, the same behaviour persisted even after adjusting the chemokine values in people that smoke who are, therefore, at higher risk of developing atherosclerotic lesions”.

“The correlation between acute heart events and higher concentrations of CCL3, further confirmed by studies we carried out in a mouse model – points out P.I. Erik A.L. Biessen, group leader at CARIM – turns out to be really important. As we performed some follow-up serum analysis we could rule out the possibility that high levels of CCL3 are related to the baseline atherosclerotic condition, proving that this marker’s concentration actually increases during the acute phase of an ischemic event. Now, what lies ahead? CCL3, as our study proves, exhibits a clear prognostic power. Monitoring its concentration during the follow-up of patients with ACS should allow the identification of those at higher risk of recurrent episodes”. Future studies are expected soon, on a wider cohort of patients. It is likely that they can reveal new and useful fluctuations of other indicators of acute heart disease.

Full article reference: de Jager S.C.A. et al.; “CCL3 (MIP-1) levels are elvated during acute coronary syndromes and show strong prognostic power for future ischemic events”. J. Mol. Cell. Cardiol. (2008), doi: 10.1016/j.yjmcc.2008.06003

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