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(Circulation Research. 2004;95:552.)
© 2004 American Heart Association, Inc.

Editorials

Macrophage-Mediated Cardiac Fibrosis

P. Christian Schulze, Richard T. Lee

From the Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Mass.

Correspondence to Richard T. Lee, MD, Cardiovascular Research, Partners Research Facility, 65 Landsdowne St, Rm 279, Cambridge, MA 02139. E-mail rlee@rics.bwh.harvard.edu

See related article, pages 637–644

Key Words: macrophage • fibrosis • regeneration

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

Both clinicians and investigators have long tended to consider cardiac fibrosis as a hopelessly unavoidable "final common pathway" of tissue injury. We are painfully familiar with the serious consequences of myocardial fibrosis, including diastolic dysfunction and promoting reentry dysrhythmias,¹ but we seem to accept that diseased myocardium eventually develops fibrosis. However, only the most advanced fibrotic tissues are lifeless; in fact, dynamic matrix turnover in fibrosing tissues is easily demonstrated, whereas the matrix of normal tissues is, in comparison, remarkably quiescent. That we can potentially steer matrix metabolism beneficially to reduce dysrhythmias or improve ventricular function is reason enough to try to understand cardiac fibrosis. In addition, as we will briefly touch on here, recent excitement in cardiac regeneration offers us yet another important reason to unravel fibrosis, because myocardial scarring may be standing in the way of successfully repairing the heart.

Treatment options to prevent cardiac fibrosis are limited and include angiotensin converting enzyme inhibitors² and aldosterone blockade.³ Matrix metalloproteinase inhibition may also reduce fibrosis.^4,5 The effects of metalloproteinase inhibition on cardiac fibrosis do not appear to be attributable to changes in collagen degradation, and there has been little recent progress on using metalloproteinase inhibition clinically. With so few weapons against cardiac fibrosis, it is therefore important to develop new strategies through understanding basic molecular pathways of matrix metabolism.

There are different types of cardiac fibrosis, and some forms of fibrosis are probably at least transiently beneficial. The fibrosis of the healing infarct in the days after myocardial infarction . . . [Full Text of this Article]

Related Article:

Overexpression of Urokinase by Macrophages or Deficiency of Plasminogen Activator Inhibitor Type 1 Causes Cardiac Fibrosis in Mice

Hideaki Moriwaki, April Stempien-Otero, Michal Kremen, Aaron E. Cozen, and David A. Dichek
Circ. Res. 2004 95: 637-644. [Abstract] [Full Text] [PDF]

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				A. Stempien-Otero, A. Plawman, J. Meznarich, T. Dyamenahalli, G. Otsuka, and D. A. Dichek Mechanisms of Cardiac Fibrosis Induced by Urokinase Plasminogen Activator J. Biol. Chem., June 2, 2006; 281(22): 15345 - 15351. [Abstract] [Full Text] [PDF]