Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality1-3 due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries. Multiple growth factors2,3 and various downstream signaling pathways involving, for example, ras4, gp-130 (ref. 4), JNK/p38 (refs. 5,6) and calcineurin/NFAT/CaMkinase7 have been implicated in the hypertrophic response. However, there is evidence that the initial phase in the development of myocardial hypertrophy involves the formation of cardiac para- and/or autocrine factors like endothelin-1, norepinephrine or angiotensin II 11 (refs. 7,8), the receptors of which are coupled to G-proteins of the Gq/11- G12/13- and GI/o-families5,6,8. Cardiomyocyte-specific transgenic overexpression of α1-adrenergic or angiotensin (AT1)-receptors as well as of the Gq αa-subunit, Gαq, results in myocardial hypertrophy9-12. These data demonstrate that chronic activation of the Gq/G11-family is sufficient to induce myocardial hypertrophy. In order to test whether Gq/G11, mediate the physiological hypertrophy response to pressure overload, we generated a mouse line lacking both Gαq and Gα11 in cardiomyocytes. These mice showed no detectable ventricular hypertrophy in response to pressure-over-load induced by aortic constriction. The complete lack of a hypertrophic response proves that the Gq/G11-mediated pathway is essential for cardiac hypertrophy induced by pressure overload and makes this signaling process an interesting target for interventions to prevent myocardial hypertrophy.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)