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Lipocortin 1 reduces myocardial ischemia‐reperfusion injury by affecting local leukocyte recruitment
Author(s) -
D’ Amico Michele,
Di Filippo Clara,
La Mylinh,
Solito Egle,
McLean Peter G.,
JFlower Roderick J.,
Oliani Sonia M,
Perretti Mauro
Publication year - 2000
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.99-0602fje
Subject(s) - myeloperoxidase , ischemia , annexin , chemistry , medicine , inflammation , endocrinology , apoptosis , biochemistry
We assessed here the effect of the glucocorticoid‐regulated protein lipocortin 1 (LC1) in a model of rat myocardial ischemia reperfusion. Treatment of animals with human recombinant LC1 at the end of a 25‐min ischemic period significantly reduced the extent of infarct size in the area at risk as measured 2 h later, with ~50% inhibition at the highest dose tested of 50 per rat (equivalent to 5.4 nmol/kg). The protective effect of LC1 was abolished by protein denaturation and not mimicked by the structurally related protein annexin V. A combination of electron and light microscopy techniques demonstrated the occurrence of the myocardial damage at the end of the reperfusion period, with loss of fiber organization. LC1 provided a partial and visible protection. The dose‐dependent protection afforded by LC1 was paralleled by lower values of myeloperoxidase activity, tumor necrosis factor α, and macrophage inflammatory protein‐1α. The functional link between migrated leukocytes and the myocardial damage was confirmed by electron and light microscopy, and a significantly lower number of extravasated leukocytes was counted in the group of rats treated with LC1 (50 μg). In conclusion, we demonstrate for the first time that LC1 reduces the leukocyte‐dependent myocardial damage associated with an ischemia‐reperfusion procedure.