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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)

From: Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies

  Increased function Decreased function
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
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
  1. Most data on N-Ras come from clinical reports. There are no clinical reports of decreased function of H-, K- or N-Ras