Small GTP-binding proteins and their regulators in cardiac hypertrophy

Small GTP-binding proteins (small G proteins) act as GDP–GTP-regulated molecular switches and are activated by guanine nucleotide exchange factors (GEFs) in response to diverse extracellular stimuli. During this last decade, numerous molecular and cellular studies, as well as genetically-modified animal models, have highlighted the role of small G proteins in the regulation of cardiac hypertrophy. The growing interest in small G protein signalling comes from the fact that chronic hypertrophic response is considered maladaptive and predisposes individuals to heart failure. Although some of the hypertrophic signalling pathways involving small G proteins have now been identified, a central question deals with the identity of the GEFs that modulate small G protein activation in the context of cardiac hypertrophy. Here, we discuss the precise regulation of Ras and Rho subfamilies of GTPases by GEFs and other regulatory proteins during cardiac hypertrophy. In addition, we summarize recent published data, mainly those describing the role of small G proteins in the development of myocardial hypertrophy and we further present the importance of their downstream effectors in myocardial remodelling.