Chemokines and Atherosclerotic Plaque Progression: Towards Therapeutic Targeting?

Author(s): A. O. Kraaijeveld , S. C. A. de Jager , T. J. C. van Berkel , E. A. L. Biessen , J. W. Jukema .

Journal Name: Current Pharmaceutical Design

Volume 13 , Issue 10 , 2007

Abstract:

Atherosclerosis is currently viewed as an inflammatory disease in which the initiation and progression of the atherosclerotic plaque towards a rupture prone, unstable plaque is driven by leukocyte recruitment mediated by various inflammatory mediators. Recently, interest in chemotactic cytokines or chemokines with regard to atherosclerosis has been growing as chemokines mediate the influx of leukocytes that is typical of atherothrombosis. The activity of the majority of chemokines is overlapping and chemokines are not only produced by the various cellular constituents of the atherosclerotic plaque but also by activated platelets. Consequently, the direct influence of individual chemokines on plaque destabilisation and rupture is widespread and rather unclear. Experimental research has already established the role of a number of chemokines in advanced atherosclerosis. Nevertheless, given the complexity and size of the chemokine family, further screening of cardiovascular disease for chemokine level and genetic polymorphisms for chemokines will be warranted as the search for viable biomarkers of plaque destabilization as well as novel therapeutic targets for specific atheroregressive therapeutic compounds is ongoing. With regard to the latter, clinical trials with specific chemokine inhibitory strategies, like chemokine receptor antagonists, are already underway in other inflammatory disorders. Summarizing, chemokine inhibition likely constitutes an important therapeutic option next to already established drugs in the management of cardiovascular disease.

Keywords: Atherosclerosis, chemokines, vulnerable plaque, cardiovascular diseases, leukocytes, platelets, therapeutics

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Article Details

VOLUME: 13
ISSUE: 10
Year: 2007
Page: [1039 - 1052]
Pages: 14
DOI: 10.2174/138161207780487584
Price: $58

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