|
Sign In to gain access to subscriptions and/or personal tools.
|
Blockade of calcineurin reverses cardiac hypertrophy and induces the down-regulation of JNK mRNA expression in renovascular hypertensive rats
Hongzhuan Sheng
Institute of Cardiovascular Disease Research, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China, Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China
Jianhua Zhu
Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China
Xiaohui Wu
Department of Cardiology, The Affiliated Hospital of Nantong University, Nantong 226001, China
Jinan Zhang
Institute of Cardiovascular Disease Research, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China, jinanzh506{at}yahoo.com
Introduction. Recently, calcineurin has been shown to induce cardiac hypertrophy. Mitogen-activated protein kinases (MAPK), including the extracellular-signal regulated kinases (ERK), the c-Jun NH2-terminal kinases (JNK) and the p38 MAPK (p38), have also been shown to be important in the transduction of trophic signals. The objective of this study was to investigate possible cross-talk between calcineurin and MAPK pathways in controlling renovascular hypertension-induced cardiac hypertrophy.
Methods. Renovascular hypertension was induced by the two kidney-one clip method. The left ventricular weight (LVW) and the ratio of LVW to tibial length were measured to assay the degree of cardiac hypertrophy. Calcineurin activity and MAPK mRNA expression were measured.
Results. In the left ventricle of rats with renovascular hypertension, calcineurin activity and JNK mRNA expression were increased while cardiac hypertrophy developed. Treatment with the calcineurin blocker ciclosporin A induced calcineurin inhibition and regression of cardiac hypertrophy with an improvement of cardiac diastolic function. The treatment also resulted in down-regulation of JNK mRNA expression, but the mRNA expressions of ERK and p38 were unchanged.
Conclusions. There is cross-talk between the calcineurin and JNK pathway in controlling renovascular hypertension-induced cardiac hypertrophy. Inhibition of the calcineurin and JNK pathways may be the basis of reversal of cardiac hypertrophy by calcineurin blockers.
Key Words: calcineurin • cardiac hypertrophy • mitogen-activated protein kinase • rats • renovascular hypertension
References
- Brown DW, Giles WR, Croft JB Left ventricular hypertrophy as a predictor of coronary heart disease mortality and the effect of hypertension. Am Heart J 2000;140:848-56.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Devereux RB, Roman MJ Left ventricular hypertrophy in hypertension: stimuli, patterns, and consequences. Hypertens Res 1999;22:1-9.[Web of Science][Medline]
[Order article via Infotrieve]
- Berridge MJ, Bootman MD, Lipp P. Calcium - a life and death signal. Nature 1998;395:645-8.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Crabtree G. Generic signal and specific outcome: signaling through Ca2+, calcineurin, and NF-AT. Cell 1999;96: 611-14.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Bush EW, Hood DB, Papst PJ et al. Canonical transient receptor potential channels promote cardiomyocyte hypertrophy through activation of calcineurin signaling. J Biol Chem 2006;281:33487-96.[Abstract/Free Full Text]
- Koulmann N., Novel-Chate V., Peinnequin A. et al. Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med 2006;174:699-705.[Abstract/Free Full Text]
- Sheng H., Zhu J., Wu X. et al. Angiotensin-converting enzyme inhibitor suppresses activation of calcineurin in renovascular hypertensive rats. Hypertens Res 2007;30: 1247-54.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Zobel C., Rana OR, Saygili E. et al. Mechanisms of Cadependent calcineurin activation in mechanical stretch-induced hypertrophy. Cardiology 2007;107:281-90.[CrossRef][Medline]
[Order article via Infotrieve]
- Jeong D., Kim JM, Cha H. et al. PICOT attenuates cardiac hypertrophy by disrupting calcineurin-NFAT signaling. Circ Res 2008;102:711-19.[Abstract/Free Full Text]
- Liang Q., Elson AC, Gerdes AM p38 MAP kinase activity is correlated with angiotensin II type 1 receptor blocker-induced left ventricular reverse remodeling in spontaneously hypertensive heart failure rats. J Card Fail 2006;12:479-86.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Chen S., Khan ZA, Karmazyn M. et al. Role of endothelin-1, sodium hydrogen exchanger-1 and mitogen activated protein kinase (MAPK) activation in glucose-induced cardiomyocyte hypertrophy. Diabetes Metab Res Rev 2007; 23: 356-67.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Olson AK, Protheroe KN, Segar JL, Scholz TD Mitogen-activated protein kinase activation and regulation in the pressure-loaded fetal ovine heart. Am J Physiol Heart Circ Physiol 2006;290:H1587-H1595.[Abstract/Free Full Text]
- Sopontammarak S., Aliharoob A., Ocampo C., Arcilla RA, Gupta M.P, Gupta M. Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy. Cell Biochem Biophys 2005;43:61-76.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Diedrichs H., Mei C., Frank KF, Boelck B., Schwinger RH Calcineurin independent development of myocardial hypertrophy in transgenic rats overexpressing the mouse renin gene, TGR(mREN2) 27. J Mol Med 2004;82:688-95.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Shimoyama M., Hayashi D., Zou Y. et al. Calcineurin inhibitor attenuated the development and induces the regression of cardiac hypertrophy in rats with salt-sensitive hypertension. Circulation 2000;102:1996-2004.[Abstract/Free Full Text]
- Frey N., Olson EN Cardiac hypertrophy: the good, the bad, and the ugly. Annu Rev Physiol 2003;65:45-79.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Molkentin JD, Heineke J. Regulation of cardiac hypertrophy by intracellular signaling pathways. Nat Rev Mol Cell Biol 2006;7:589-600.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Murat A., Pellieux C., Brunner HR, Pedrazzini T. CaN blockade prevents cardiac mitogen-activated protein kinase activation and hypertrophy in renovascular hypertension. J Biol Chem 2000;275:40867-73.[Abstract/Free Full Text]
- Sanna B., Bueno OF, Dai YS, Wilkins BJ, Molkentin JD Direct and indirect interactions between CaN-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol Cell Biol 2005;25:865-78.[Abstract/Free Full Text]
- Pan F., Sun L., Kardian DB, Whartenby KA, Pardoll DM, Liu JO Feedback inhibition of calcineurin and Ras by a dual inhibitory protein Carabin. Nature 2007;445:433-6.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Hill JA, Karimi M., Kutschke W. et al. Cardiac hypertrophy is not a required compensatory response to short-term pressure overload. Circulation 2000;101:2863-9.[Abstract/Free Full Text]
- Sakata Y., Masuyama T., Yamamoto K. et al. Calcineurin inhibitor attenuates left ventricular hypertrophy, leading to prevention of heart failure in hypertensive rats. Circulation 2000;102:2269-75.[Abstract/Free Full Text]
- Koulmann N., Novel-Chaté V., Peinnequin A. et al. Cyclosporin A inhibits hypoxia-induced pulmonary hypertension and right ventricle hypertrophy. Am J Respir Crit Care Med 2006;174:699-705.[Abstract/Free Full Text]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 9, No. 3,
139-145 (2008)
DOI: 10.1177/1470320308096048
 CiteULike  Complore  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter What's this?
|
|
