Figure 3.

Indirect inhibition of Rho GTPase signaling by HMG-CoA reductase inhibitors (statins). Non-cholesterol-related beneficial effects of statins mainly rest on the indirect inhibition of Rho GTPases. The statin-mediated depletion of the intracellular pool of isoprene precursors causes reduced anchorage of Rho proteins on the inner cell membrane, which impairs their activation by GEFs on this particular location. Depicted are selected cellular functions regulated by Rho GTPases that might be relevant for the heart. CHF, congestive heart failure; CR, cellular receptor; DDR, DNA damage response; FPP, farnesyl pyrophosphate; GAP, GTPase activating protein; GDP, guanosine diphosphate; GEF, guanine nucleotide exchange factor; GGP, geranylgeranyl pyrophosphate; GTP, guanosine triphosphate; NOS, nitric oxide synthase; Rho, Ras homologous proteins; ROS, reactive oxygen species; adapted from Fritz et al.¹⁵⁵