Table 1.

Studies of RAAS blockade and fibrosis inhibition

Drug	Study Type	Target Organ	Mechanism of Action	Outcome	References
Candesartan	Randomized, open-label controlled study	Liver	ARB	Reduction in αSMA, TGFβ1, Col-1, TIMP-1 and MMP2	[150]
Olmesartan, candesartan, losartan	Meta-analysis of 4 randomized controlled trials	Liver	ARB	Reduction in liver fibrosis score and area	[152]
A-779	Animal	Liver	Mas receptor antagonist	Aggravation of liver fibrosis and elevation of TGFβ	[93]
Aliskiren	In vitro	Heart, kidney	Renin inhibitor	Reduction in fibroblast proliferation, αSMA, TGFβ and collagen	[156, 159]
Candesartan	Clinical trial	Heart	ARB	Reduction of type I procollagen-Npeptide and type III procollagenN-peptide	[160]
Spironolactone	Animal	Heart, liver	Aldosterone antagonist	Reduction of TGFβ and reactive oxygen species	[151, 162, 167]
Lisinopril	Randomized clinical trial	Heart	ACE inhibitor	Reduction of myocardial fibrosis and collagen volume	[163]
Enalapril	Animal	Heart, kidney	ACE inhibitor	Reduction in fibrosis and long-term protection against organ damage	[164, 165]
Pirfenidone	Animal	Heart	Classical/alternative RAAS balance	Reduction in fibrosis	[99]
Compound 21 and A8011	In vitro	Heart, skin	AT2R agonist	Reduction in fibrosis, collagen, TIMP1, MMP1–9 and TGFβ	[171-173, 175]
Ramipril	Animal and in vitro	Skin	ACE inhibitor	Decreased collagen, TGFβ1 expression and attenuated TGFβ-activated kinase-1 phosphorylation	[145]
Topical losartan and valsartan	Pilot placebocontrolled single blinded study	Skin	ARB	Reduction in scar score	[174, 175]