Molecules linked to Ras signaling as therapeutic targets in cardiac pathologies

Biological Research

Table 2 Summary of Ras and Ras pathways modulators in the heart

Group	Molecule	Mechanism of action	References
Inhibitors of Angiotensin-II	Candesartan	Angiotensin-II AT1R receptor antagonist	Established therapy of clinical cardiac hypertrophy and HF
Inhibitors of Angiotensin-II	Captopril	Angiotensin-converting enzyme (ACE) inhibitor	Established therapy of clinical cardiac hypertrophy and HF
Inhibitors of Ras farnesylation	Statins	Inhibits synthesis of farnesyl by inhibition of HMG-CoA reductase	Lipid lowering therapy with broad clinical applications in cardiovascular prevention
	Farnesyl transferase siRNA	Inhibits expression of farnesyl transferase	Improves pressure overload cardiac remodeling in mice [100]
	FPT-III	Farnesyl analog: inhibits farnesylation of Ras and other small GTPases	Cardioprotective effect in ischemia–reperfusion related to ischemic pre-conditioning [90]
	FTI-276	Tetrapeptid-mimetic, which inhibits FPPS	Improved cardiac remodeling in spontaneously hypertensive rats [101]
Silencing-mRNA	si-RNA-H-Ras	Inhibits mRNA synthesis of H-Ras	Inhibits cardiomyocyte hypertrophy in vitro by phenylephrine [25]
Signal inhibitors	Cyclosporin A	Calcineurin inhibitor	Attenuates pressure overload cardiac hypertrophy but causes HF [106]
	Rapamycin	Akt inhibitor	Prevented cardiac hypertrophy in a transgenic mouse model with SHP-2 active mutation [107]
	PD0325901	MEK inhibitor	Tested in cancer patients [111]
	SB203580	p38 inhibitor	Only tested in cancer cells

Examples of molecules used to inhibit Ras and its pathways in the heart, experimentally in animal models or clinically in patients. To our knowledge, the anti-cancer molecules PD0325901 and SB203580 have not yet been used in cardiac diseases, but are of interest as inhibitors of Ras-related pathways (more details in paragraph 6 of the article)

ISSN: 0717-6287