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(Circulation. 2005;111:391-393.)
© 2005 American Heart Association, Inc.

Editorial

Gene Therapy for Repair of Cardiac Fibrosis

A Long Way to Tipperary

Maurits Allessie, MD, PhD; Ulrich Schotten, MD, PhD; Sander Verheule, PhD; Erik Harks, PhD

From the Department of Physiology, Cardiovascular Institute Maastricht, University of Maastricht (M.A., U.S., S.V., E.H.), Maastricht, and the Royal Netherlands Academy of Arts and Sciences (M.A.), Amsterdam, the Netherlands.

Correspondence to Prof M.A. Allessie, Department of Physiology, Cardiovascular Research Institute Maastricht, University of Maastricht, PO Box 616, 6200 MD Maastricht, The Netherlands. E-mail m.allessie@fys.unimaas.nl

Key Words: Editorials • aging • calcium • fibrillation • gene therapy

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

Because of the increase in life expectancy and a high survival rate after myocardial infarction, cardiac fibrosis is becoming one of the most important problems in cardiology. It is characterized by excessive accumulation of fibrillar collagen in the extracellular space, either because of a loss of cardiomyocytes (replacement fibrosis) and/or as an interstitial response to various chronic cardiovascular diseases such as hypertension, myocarditis, and congestive heart failure (reactive fibrosis).¹ In humans, cardiac fibrosis is universal in the aging heart. Activated fibroblasts play a pivotal role in the formation and maintenance of fibrous tissue by the production of various extracellular-matrix proteins, including collagen and fibronectin. It is now recognized that even in areas with long-standing fibrosis, such as postinfarction scars, fibroblasts remain metabolically active.² Their activity is regulated by various autocrine and paracrine factors, such as angiotensin II, aldosterone, endothelins, cytokines, and growth factors.³ The renin-angiotensin-aldosterone system is considered to be of major importance for the regulation of cardiac fibrosis. Increased tissue levels of angiotensin II have shown to promote, and ACE inhibitors are able to delay the development of, cardiac fibrosis.^4,5

See p 394

Interstitial fibrosis reduces the electrical coupling between cardiac myocytes because fibroblasts produce smaller or larger collagenous septa, which electrically insulate cardiac cells or muscle bundles. As a result, the normal myocardial architecture becomes disrupted and is transformed into a pathological substrate characterized by the presence of multiple insulating barriers, which force the depolarization wave to spread nonuniformly. As predicted by computer simulations and demonstrated in cell . . . [Full Text of this Article]

Related Article:

Fibroblasts Can Be Genetically Modified to Produce Excitable Cells Capable of Electrical Coupling

Eddy Kizana, Samantha L. Ginn, David G. Allen, David L. Ross, and Ian E. Alexander
Circulation 2005 111: 394-398. [Abstract] [Full Text]

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