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(Circulation Research. 2007;101:328.)
© 2007 American Heart Association, Inc.

Editorials

Profilin-1

An Unexpected Molecule Linking Vascular Inflammation to the Actin Cytoskeleton

Anton J.G. Horrevoets

From the Department of Medical Biochemistry, Academic Medical Center, University of Amsterdam, The Netherlands.

Correspondence to Anton J.G. Horrevoets, PhD, Medical Biochemistry, Room K1-114, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. E-mail a.j.horrevoets@amc.uva.nl

See related articles, pages 357–367

Key Words: atherosclerosis • endothelium • inflammation • macrophages • hemodynamics

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Endothelial dysfunction, as defined by a decreased bioavailability of NO, is one of the earliest steps in the development of atherosclerosis.^1,2 The resulting vascular inflammation including accumulation of lipid-laden macrophages hallmarks the pathology underlying the major clinical complications of cardiovascular disease. Many of the key players in these inflammatory events have been identified and validated in vivo, with a clear focus on the endothelial adhesion molecules like VCAM-1, the macrophage lipid handling machinery and inflammatory mediators like various chemokines that attract a variety of leukocytes to the atherosclerotic lesion.³ In the current issue of Circulation Research, Romeo et al⁴ identify a quite unexpected protein to play a pivotal role in these processes. Mice with a partial deletion of profilin-1 (Pfn1), an actin binding molecule that is involved in the dynamics of the actin cytoskeleton (Figure), are shown to be substantially protected against atherosclerosis. This is the second example for a prominent role of an actin binding molecule in cardiovascular disease, given the recent excitement regarding the potential implication for regenerative medicine of thymosin beta-4 (Figure 1), because of its action in preventing ischemic damage to myocardium and inducing cardiac neovascularization.^5,6

View larger version (22K):   The pivotal role of profilin-1 in actin dynamics and its cardiovascular effects. Profilin-1 greatly increases the rate of actin polymerization by both binding actin-ADP to catalyze nucleotide exchange to yield actin-ATP and by acting as the substrate of the processive actin-polymerising enzyme Formin, which adds actin-ATP to the barbed ends of (newly) formed . . . [Full Text of this Article]