Biochemical and Biophysical Research Communications
JNK1 is required to preserve cardiac function in the early response to pressure overload
Section snippets
Materials and methods
Experimental animals. JNK1−/−, JNK2−/−, and JNK3−/− mice were described previously [15], [16], [17]. Adult wild-type (WT) and knockout mice of either gender, 3 months of age were used for this study. The animals in the present study were handled according to approved protocols of the Institutional Review Board at Duke University Medical Center.
Echocardiography. Serial transthoracic M-mode echocardiography was performed on conscious mice with an HDI 5000 echocardiograph (ATL, Bothell,
Results
To determine the role of JNKs in the induction of cardiac hypertrophy, we applied pressure overload by transverse aortic constriction (TAC) for 7 days on knockout mice with selective deletion in each of the three JNK genes (JNK1−/−, JNK2−/−, and JNK3−/−). At sacrifice, no significant differences were observed in the trans-stenotic pressure gradients between JNK knockout mice and their WT littermates (systolic pressure gradient: WT = 80 ± 6 mmHg; JNK1−/− = 76 ± 7 mmHg; JNK2−/− = 77 ± 9 mmHg; JNK3−/− = 93 ± 8 mmHg).
Discussion
In this study, we tested the role of specific members of the JNK family in the development of cardiac hypertrophy and failure in response to pressure overload. Our data show that none of the JNK isoforms are individually required for the development of cardiac hypertrophy. In contrast, JNK1 has a specific role in preserving cardiac function in the early response to hemodynamic overload. Our results support the concept that JNK1 plays a specific role in cardioprotection by inhibiting
Acknowledgment
We thank Anne M. Pippen for her excellent technical assistance. This work was supported, in part, by Grant NIH HL 56687 to Howard A. Rockman.
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- 1
These two authors equally contributed to this work.
- 2
Present address: Clinical Research and Development, Novartis Pharma K.K., Minato-ku, Tokyo, Japan.
- 3
Present address: Department of Cardiology, Kobe Redcross Hospital, Kobe, Japan.