Journal ArticleDOI
Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure.
Stephane Heymans,Aernout Luttun,Dieter Nuyens,Gregor Theilmeier,Esther E. Creemers,Lieve Moons,G D Dyspersin,Jack P.M. Cleutjens,M Shipley,A Angellilo,Marcel Levi,O Nübe,Andrew Baker,Eli Keshet,Florea Lupu,Jean-Marc Herbert,Jos F.M. Smits,Steven D. Shapiro,Myriam Baes,Marcel Borgers,Desire Collen,Mat J.A.P. Daemen,Peter Carmeliet +22 more
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TLDR
Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.Abstract:
Cardiac rupture is a fatal complication of acute myocardial infarction lacking treatment. Here, acute myocardial infarction resulted in rupture in wild-type mice and in mice lacking tissue-type plasminogen activator, urokinase receptor, matrix metalloproteinase stromelysin-1 or metalloelastase. Instead, deficiency of urokinase-type plasminogen activator (u-PA–/–) completely protected against rupture, whereas lack of gelatinase-B partially protected against rupture. However, u-PA–/– mice showed impaired scar formation and infarct revascularization, even after treatment with vascular endothelial growth factor, and died of cardiac failure due to depressed contractility, arrhythmias and ischemia. Temporary administration of PA inhibitor-1 or the matrix metalloproteinase-inhibitor TIMP-1 completely protected wild-type mice against rupture but did not abort infarct healing, thus constituting a new approach to prevent cardiac rupture after acute myocardial infarction.read more
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Angiogenesis in cancer and other diseases
Peter Carmeliet,Rakesh K. Jain +1 more
TL;DR: Pathological angiogenesis is a hallmark of cancer and various ischaemic and inflammatory diseases and integrated understanding is leading to the development of a number of exciting and bold approaches to treat cancer and other diseases, but owing to several unanswered questions, caution is needed.
Journal ArticleDOI
Mechanisms of angiogenesis and arteriogenesis.
TL;DR: The cellular and molecular mechanisms underlying the formation of endothelium-lined channels and their maturation via recruitment of smooth muscle cells (arteriogenesis) during physiological and pathological conditions are summarized, alongside with possible therapeutic applications.
Journal ArticleDOI
How Matrix Metalloproteinases Regulate Cell Behavior
Mark D. Sternlicht,Zena Werb +1 more
TL;DR: Recent advances shed light on how the structure and function of the MMPs are related and on how their transcription, secretion, activation, inhibition, localization, and clearance are controlled.
Journal ArticleDOI
Structure and function of matrix metalloproteinases and TIMPs
TL;DR: The members of the MMP family are introduced and their domain structure and function, proenyme activation, the mechanism of inhibition by TIMPs and their significance in physiology and pathology are discussed.
Journal ArticleDOI
Neovascularization of ischemic myocardium by human bone-marrow–derived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function
Alfred Kocher,Michael D. Schuster,Matthias Szabolcs,Shin Takuma,Daniel Burkhoff,Jennifer Wang,Shunichi Homma,Niloo M. Edwards,Silviu Itescu +8 more
TL;DR: It is shown that bone marrow from adult humans contains endothelial precursors with phenotypic and functional characteristics of embryonic hemangioblasts, and that these can be used to directly induce new blood vessel formation in the infarct-bed and proliferation of preexisting vasculature after experimental myocardial infarction.
References
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Journal ArticleDOI
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