Targeted deletion of caspase-1 reduces early mortality and left ventricular dilatation following myocardial infarction.

@article{citeulike:2949823, abstract = {Objective. - Mice with targeted deletion of caspase-1 (interleukin-1beta (IL-1beta)-converting enzyme) lack the active forms of IL-1beta and IL-18, two cytokines implicated in maladaptive ventricular remodeling following cardiac injury. We, therefore, investigated the extent of ventricular dilation in caspase-1-knockout (KO) mice.Methods and results. - Transthoracic echocardiography was performed at days 1, 4, and 9 following left anterior descending artery ligation in caspase-1-KO and wild-type (WT) control animals, including M-mode and short-axis imaging at both mid-papillary and apical levels. Although initial post-operative mortality was lower in KO than in WT animals (21.4\% WT, 12.0\% KO, P < 0.001), there was no difference in mortality between 24 h and 9 d (P = n.s.). Caspase-1 KOs exhibited significantly less mid-papillary ventricular dilatation at days 4 and 9 compared to day 1 post-myocardial infarction (MI) (P < 0.05). Caspase-1 KOs also had a marked (50\%) reduction in the level of matrix metalloproteinase 3 (MMP-3), although no significant changes occurred in other MMPs or in tissue inhibitors of metalloproteinase 1 levels by immunoblot analysis. Although IL-beta plasma levels were not detectable, both IL-18 levels and the rate of apoptosis in remodeling, non-infarcted muscle were significantly higher in WT compared to caspase-1-KO animals.Conclusion. - Mice lacking caspase-1 exhibited both improved peri-infarct survival and a decreased rate of ventricular dilatation, possibly due in part to a decrease in MMP-3 activity, IL-18 production, and a reduction in the rate of apoptosis after experimental MI.}, address = {Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, MA 02115, Boston, USA. S.frantz@mail.uni-uerzburg.de}, author = {Frantz, S. and Ducharme, A. and Sawyer, D. and Rohde, L. E. and Kobzik, L. and Fukazawa, R. and Tracey, D. and Allen, H. and Lee, R. T. and Kelly, R. A. }, citeulike-article-id = {2949823}, issn = {0022-2828}, journal = {Journal of molecular and cellular cardiology}, keywords = {cardiac-hypertrophy, caspase-1, il-18, myocardial-infarction}, month = {June}, number = {6}, pages = {685--694}, posted-at = {2008-07-02 04:25:47}, priority = {2}, title = {Targeted deletion of caspase-1 reduces early mortality and left ventricular dilatation following myocardial infarction.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12788386}, volume = {35}, year = {2003} }

TY - JOUR ID - citeulike:2949823 L3 - citeulike-article-id:2949823 TI - Targeted deletion of caspase-1 reduces early mortality and left ventricular dilatation following myocardial infarction. JF - Journal of molecular and cellular cardiology VL - 35 IS - 6 SP - 685 EP - 694 AD - Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, MA 02115, Boston, USA. S.frantz@mail.uni-uerzburg.de SN - 0022-2828 N2 - Objective. - Mice with targeted deletion of caspase-1 (interleukin-1beta (IL-1beta)-converting enzyme) lack the active forms of IL-1beta and IL-18, two cytokines implicated in maladaptive ventricular remodeling following cardiac injury. We, therefore, investigated the extent of ventricular dilation in caspase-1-knockout (KO) mice.Methods and results. - Transthoracic echocardiography was performed at days 1, 4, and 9 following left anterior descending artery ligation in caspase-1-KO and wild-type (WT) control animals, including M-mode and short-axis imaging at both mid-papillary and apical levels. Although initial post-operative mortality was lower in KO than in WT animals (21.4% WT, 12.0% KO, P < 0.001), there was no difference in mortality between 24 h and 9 d (P = n.s.). Caspase-1 KOs exhibited significantly less mid-papillary ventricular dilatation at days 4 and 9 compared to day 1 post-myocardial infarction (MI) (P < 0.05). Caspase-1 KOs also had a marked (50%) reduction in the level of matrix metalloproteinase 3 (MMP-3), although no significant changes occurred in other MMPs or in tissue inhibitors of metalloproteinase 1 levels by immunoblot analysis. Although IL-beta plasma levels were not detectable, both IL-18 levels and the rate of apoptosis in remodeling, non-infarcted muscle were significantly higher in WT compared to caspase-1-KO animals.Conclusion. - Mice lacking caspase-1 exhibited both improved peri-infarct survival and a decreased rate of ventricular dilatation, possibly due in part to a decrease in MMP-3 activity, IL-18 production, and a reduction in the rate of apoptosis after experimental MI. KW - cardiac-hypertrophy KW - caspase-1 KW - il-18 KW - myocardial-infarction AU - Frantz, S AU - Ducharme, A AU - Sawyer, D AU - Rohde, LE AU - Kobzik, L AU - Fukazawa, R AU - Tracey, D AU - Allen, H AU - Lee, RT AU - Kelly, RA PY - 2003/06// UR - http://view.ncbi.nlm.nih.gov/pubmed/12788386 ER -