Universität zu Köln

Lauten, Alexander, Gerhard-Garcia, Alexandra, Suhr, Frank, Fischer, Juergen H., Figulla, Hans R. and Bloch, Wilhelm (2014). Impact of Ischemia-Reperfusion on Extracellular Matrix Processing and Structure of the Basement Membrane of the Heart. PLoS One, 9 (3). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

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Abstract

Purpose: Acute ischemic injury is a strong inductor of cardiac remodelling, resulting in structural changes of the extracellular matrix (ECM) and basement membrane (BM). In a large animal model of ischemia-reperfusion (I/R) we investigated the post-ischemic liberation of the collagen-IV-fragments Tumstatin (TUM; 28 kDa-fragment of collagen-IV-alpha-3), Arresten (ARR; 26 kDa-fragment of collagen-IV-alpha-1) and Endorepellin (LG3, 85 kDa-fragment of perlecan) which are biologically active in angiogenesis and vascularization in the post-ischemic myocardium. Methods and Results: In this blinded study, 30 pigs were randomized to 60 min of global I/R at either 4 degrees C or 32 degrees C or served as control. Three transmyocardial tissue samples were collected prior to ischemia and within 30 min and 150 min of reperfusion. Tissue content of TUM, ARR and LG3 was analyzed by western blotting and immunostaining. Within 150 min of mild hypothermic I/R a significantly increased tissue content of ARR (0.17+/-0.14 vs. 0.56+/-0.56; p = 0.001) and LG3 (1.13+/-0.34 vs. 2.51+/-1.71, p<0.001) was observed. In contrast, deep hypothermic I/R was not associated with a significant release of cleavage products. Cleavage of TUM remained unchanged irrespective of temperature. Increased matrix processing following mild hypothermia I/R is further supported by a>11 fold elevation of creatine kinase (2075+/-2595 U/l vs. 23248+/-6551 U/l; p<0.001) in the coronary sinus plasma samples. Immunostaining demonstrated no changes for ARR and LG3 presentation irrespective of temperature. In contrast, TUM significantly decreased in the BM surrounding cardiomyocytes and capillaries after mild and deep hypothermic I/R, thus representing structural alterations of the BM in these groups. Conclusion: The study demonstrates an early temperature-dependent processing of Col-IV as major component of the BM of cardiomyocytes and vascular endothelium. These observations support the protective effects of deep hypothermia during I/R. Furthermore, the results suggest an increased structural remodelling of the myocardial basement membrane with potential functional impairment during mild hypothermic I/R which may contribute to the progression to post-ischemic heart failure.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lauten, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerhard-Garcia, Alexandra UNSPECIFIED UNSPECIFIED UNSPECIFIED Suhr, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Juergen H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Figulla, Hans R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bloch, Wilhelm UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-443086
DOI:	10.1371/journal.pone.0092833
Journal or Publication Title:	PLoS One
Volume:	9
Number:	3
Date:	2014
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1932-6203
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ANGIOGENESIS; METALLOPROTEINASES; ENDOSTATIN; INFARCTION; CONDUCTION; ENDOREPELLIN; PROTEOLYSIS; INHIBITION; TUMSTATIN; FRAGMENT Multiple languages Multidisciplinary Sciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/44308