BACKGROUND AND PURPOSE: Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH: Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at days 7, 36 and 70. KEY RESULTS: Over the 9 weeks, mortality was not different between the groups. On echocardiography, animals after myocardial infarction exhibited significant left ventricular dilatation as expected (week 10, end-systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm). However, there was no difference between placebo and SB 239063-treated rats (week 10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no effect on left ventricular hypertrophy. Treatment with SB 239063 significantly reduced cytokine expression of tumour necrosis factor and interleukin-1beta after myocardial infarction. However, collagen content was not influenced by the treatment. CONCLUSION: Despite a reduction of inflammation, treatment with the p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function when treatment is started 7 days after myocardial infarction.
BACKGROUND AND PURPOSE: Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats. EXPERIMENTAL APPROACH: Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery. Serial transthoracic echocardiography was performed at days 7, 36 and 70. KEY RESULTS: Over the 9 weeks, mortality was not different between the groups. On echocardiography, animals after myocardial infarction exhibited significant left ventricular dilatation as expected (week 10, end-systolic diameter, placebo sham 5.21+/- 0.34 vs. placebo MI 8.44+/- 0.57 mm). However, there was no difference between placebo and SB 239063-treated rats (week 10, end-systolic diameter, SB MI 7.76+/- 0.74 mm, not significantly different from placebo MI). Haemodynamics changed accordingly. Moreover, SB 239063 had no effect on left ventricular hypertrophy. Treatment with SB 239063 significantly reduced cytokine expression of tumour necrosis factor and interleukin-1beta after myocardial infarction. However, collagen content was not influenced by the treatment. CONCLUSION: Despite a reduction of inflammation, treatment with the p38 inhibitor SB 239063 does not affect cardiac remodelling and cardiac function when treatment is started 7 days after myocardial infarction.
Authors: Feng Gao; Tian-Li Yue; Dong-Wei Shi; Theodore A Christopher; Bernard L Lopez; Eliot H Ohlstein; Frank C Barone; Xin L Ma Journal: Cardiovasc Res Date: 2002-02-01 Impact factor: 10.787
Authors: F C Barone; E A Irving; A M Ray; J C Lee; S Kassis; S Kumar; A M Badger; R F White; M J McVey; J J Legos; J A Erhardt; A H Nelson; E H Ohlstein; A J Hunter; K Ward; B R Smith; J L Adams; A A Parsons Journal: J Pharmacol Exp Ther Date: 2001-02 Impact factor: 4.030
Authors: T M Behr; S S Nerurkar; A H Nelson; R W Coatney; T N Woods; A Sulpizio; S Chandra; D P Brooks; S Kumar; J C Lee; E H Ohlstein; C E Angermann; J L Adams; J Sisko; J D Sackner-Bernstein; R N Willette Journal: Circulation Date: 2001-09-11 Impact factor: 29.690
Authors: P Liao; D Georgakopoulos; A Kovacs; M Zheng; D Lerner; H Pu; J Saffitz; K Chien; R P Xiao; D A Kass; Y Wang Journal: Proc Natl Acad Sci U S A Date: 2001-10-02 Impact factor: 11.205
Authors: Stefan Frantz; Kai Hu; Julian Widder; Barbara Bayer; Catharina Clara Witzel; Isabel Schmidt; Paolo Galuppo; Jörg Strotmann; Georg Ertl; Johann Bauersachs Journal: Br J Pharmacol Date: 2003-12-08 Impact factor: 8.739
Authors: Diana A Gorog; Masaya Tanno; Xuebin Cao; Mohamed Bellahcene; Rekha Bassi; Alamgir M N Kabir; Kushal Dighe; Roy A Quinlan; Michael S Marber Journal: Cardiovasc Res Date: 2004-01-01 Impact factor: 10.787
Authors: Kumar Kotlo; Keven R Johnson; Jean M Grillon; David L Geenen; Pieter deTombe; Robert S Danziger Journal: J Proteomics Date: 2012-05-31 Impact factor: 4.044