Table 1 Summary of H, K and N-Ras mutants with gain or loss of function, in vitro (cardiomyocytes in culture) and in vivo (rodent models and clinical syndromes)

H-Ras

In vitro: Ras Val12 [25, 28]:

  Hypertrophy with sarcomeric disruption

  Inhibition of cardiomyocyte beating

In vivo: Ras Val12 in mice [12, 41]:

  Hypertrophic cardiomyopathy

  H-Ras wild type compensates K-Ras^−/− in mice

Clinical: Costello syndrome [81]

  Hypertrophic cardiomyopathy

  Arrhythmias

In vitro: DN-Ras [25]:

  Enhancement of cardiomyocyte beating

  Enhancement of sarcomeric structure

In vivo: experiments of H-Ras inhibition [25, 33]:

  DN-Ras favors physiological cardiac hypertrophy in a rat model of pressure overload

  Potential therapy for pathological cardiac hypertrophy and heart failure

  H-Ras^−/− mice: normal heart and offsprings

Clinical: no data

K-Ras

In vitro: Active K-Ras V14I in cardiomyocyte [34]:

  Increased mitosis

In vivo: K-Ras V14I mice [34]:

  Hyperplasia with no hypertrophy

Clinical: Noonan or cardio-facio-cutaneous syndromes [80]:

  Hypertrophic cardiomyopathy

  Atrial and ventricular septal defects

  Pulmonary valve stenosis

In vitro: No data

In vivo: K-Ras^−/− mice [33, 35]:

  Very low proliferation of cardiomyocytes, lethal at embryonic day 15.5 with extremely thin ventricular walls

  K-Ras is the only essential gene in the Ras subfamily

  K-Ras ^± mice: normal at birth and protected in pressure overload

Clinical: no data

N-Ras

In vitro: No data on cardiac cells

In vivo: N-Ras G12D mice [110]

 Mutated mouse embryos with cardiac malformations mimicking Noonan Syndrome: ventricular septal defects, double outlet right ventricle, hypertrabeculated/thin myocardium and pulmonic valve stenosis

Clinical: Noonan syndrome—some cases [37]

In vitro: No data

In vivo: N-Ras^−−/− mice [33]:

Normal heart, normal offsprings

Clinical: no data