Decreased Plasminogen Activator Inhibitor and Tissue Metalloproteinase Inhibitor Expression May Promote Increased Metalloproteinase Activity with Increasing Duration of Human Atrial Fibrillation

Autor:	Felix Gramley, Michael Schmid, Mindaugas Rakauskas, Patrick Schauerte, Karl Mischke, Peter Hanrath, Jurgita Plisiene, Christian Knackstedt, Malte Kelm, Johann Lorenzen, Axel Gressner, Rimantas Benetis, Thomas Schimpf, Rüdiger Autschbach
Rok vydání:	2007
Předmět:	Male medicine.medical_specialty Time Factors Matrix metalloproteinase Pathogenesis Fibrosis Physiology (medical) Internal medicine Atrial Fibrillation Renin–angiotensin system medicine Humans Sinus rhythm Aged Fibrillation business.industry Tissue Inhibitor of Metalloproteinases Atrial fibrillation Middle Aged medicine.disease Matrix Metalloproteinases Enzyme Activation Plasminogen Inactivators Endocrinology Gene Expression Regulation Female medicine.symptom Cardiology and Cardiovascular Medicine business Plasminogen activator
Zdroj:	Journal of Cardiovascular Electrophysiology. 18:1076-1082
ISSN:	1540-8167 1045-3873
DOI:	10.1111/j.1540-8167.2007.00906.x
Popis:	Introduction: Atrial fibrosis has been shown to concur with the persistence of atrial fibrillation (AF) and is only incompletely reversible, thus counteracting attempts to restore and maintain sinus rhythm (SR). Besides the angiotensin system, the matrix metalloproteinases (MMP) play a major role in the pathogenesis of fibrosis. Thus, the present study investigated changes of the MMP system during the development of human AF. Methods and Results: Right atrial appendages of 146 patients were excised during heart surgery and grouped according to rhythm (SR vs AF) and AF duration. Hydroxyproline as a surrogate for collagen content and morphometrically determined collagen content increased significantly from SR (14.3 ± 7.7%) to chronic permanent AF (CAF) of 6–24 months (21.2 ± 9.2%, P = 0.02), and CAF of > 60 months (25.3 ± 4.7%, P < 0.01). From SR to paroxysmal and chronic persistent AF (CPAF) and to CAF MMP-2 and MMP-9 activity rose, while their mRNA and protein levels were not altered significantly. Plasminogen activator inhibitor (PAI), an inhibitor of a potent activator of many MMPs, was significantly decreased with increasing duration of AF. In parallel, the mRNA levels of the tissue inhibitors of MMPs TIMP-1 and -2 decreased significantly. Conclusion: Human atrial fibrogenesis is enhanced with increasing duration of AF: a longer AF duration is associated with elevated atrial interstitial MMP activity, but decreased PAI and TIMP expression.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88f6e8fe9766f49255ff75f13053c5ba https://doi.org/10.1111/j.1540-8167.2007.00906.x Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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