Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
Medientyp:
E-Artikel
Titel:
MMP-2: is too low as bad as too high in the cardiovascular system?
Beteiligte:
Hardy, Eugenio;
Hardy-Sosa, Anette;
Fernandez-Patron, Carlos
Erschienen:
American Physiological Society, 2018
Erschienen in:
American Journal of Physiology-Heart and Circulatory Physiology, 315 (2018) 5, Seite H1332-H1340
Sprache:
Englisch
DOI:
10.1152/ajpheart.00198.2018
ISSN:
0363-6135;
1522-1539
Entstehung:
Anmerkungen:
Beschreibung:
Matrix metalloproteinase (MMP)-2 cleaves a broad spectrum of substrates, including extracellular matrix components (responsible for normal tissue remodeling) and cytokines (modulators of the inflammatory response to physiological insults such as tissue damage). MMP-2 expression is elevated in many cardiovascular pathologies (e.g., myocardial infarction, hypertensive heart disease) where tissue remodeling and inflammatory responses are perturbed. Thus, it has generally been assumed that blockade of MMP-2 activity will yield therapeutic effects. Here, we provide a counterargument to this dogma based on 1) preclinical studies on Mmp2-null ( Mmp2−/−) mice and 2) clinical studies on patients with inactivating MMP2 gene mutations. Furthermore, we put forward the hypothesis that, when MMP-2 activity falls below baseline, the bioavailability of proinflammatory cytokines normally cleaved and inactivated by MMP-2 increases, leading to the production of cytokines and cardiac secretion of phospholipase A2activity into the circulation, which stimulate systemic inflammation that perturbs lipid metabolism in target organs. Finally, we suggest that insufficient understanding of the consequences of MMP-2 deficiency remains a major factor in the failure of MMP-2 inhibitor-based therapeutic approaches. This paucity of knowledge precludes our ability to effectively intervene in cardiovascular and noncardiovascular pathologies at the level of MMP-2.