Chemokines are a family of chemotactic cytokines that play an essential role in leukocyte trafficking. Upregulation of both CC
and CXC chemokines is a hallmark of the inflammatory and reparative response following myocardial infarction. Release of danger signals
from dying cells and damaged extracellular matrix activates innate immune pathways that stimulate chemokine synthesis. Cytokineand
chemokine-driven adhesive interactions between endothelial cells and leukocytes mediate extravasation of immune cells into the infarct.
CXC chemokines (such as interleukin-8) are bound to glycosaminoglycans on the endothelial surface and activate captured neutrophils,
inducing expression of integrins. CC chemokines (such as monocyte chemoattractant protein (MCP)-1) mediate recruitment of proinflammatory
and phagocytotic mononuclear cells into the infarct. CC Chemokines may also regulate late infiltration of the healing infarct
with inhibitory leukocytes that suppress inflammation and restrain the post-infarction immune response. Non-hematopoietic cells
are also targeted by chemokines; in healing infarcts, the CXC chemokine Interferon- inducible Protein (IP)-10 exerts antifibrotic actions,
inhibiting fibroblast migration. Another member of the CXC subfamily, Stromal cell-derived Factor (SDF)-1, may protect the infarcted
heart by activating pro-survival signaling in cardiomyocytes, while exerting angiogenic actions through chemotaxis of endothelial progenitors.
Several members of the chemokine family may be promising therapeutic targets to attenuate adverse remodeling in patients with
Keywords: Leukocyte, chemokine, cytokine, myocardial infarction, cardiac remodeling, fibrosis, monocyte chemoattractant protein-1.
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Published on: 01 April, 2014
Page: [1971 - 1979]