Investigational drugs targeting cardiac fibrosis.
Fibrosis is an accumulation of proteins including collagen in the extracellular space, which has previously been considered as irreversible damage in various cardiovascular diseases including heart failure and hypertension. The pathophysiology of fibrosis is currently better understood and can be evaluated by non-invasive methods. Here, the authors present briefly the impact and molecular mechanisms of fibrosis in the myocardium and the promising therapeutic candidates including anti-hypertensive therapies, heart-rate lowering drugs, anti-inflammatory agents, as well as other innovative approaches such as inhibitors of growth factors, miRNA or cell therapy. Surrogate end points allow for larger clinical trials than previously possible with endomyocardial biopsies, and magnetic resonance and molecular imaging should open new fields of research on cardiac fibrosis. Several pre-clinical findings are very promising, and some clinical data support the proofs of concept, mainly those with inhibitors of the renin-angiotensin system. These approaches open the field for regression of fibrosis and include the following: first, some of these drugs are widely used like renin-angiotensin system inhibitors; second, inflammation modulators; third, in near future entirely new approaches targeting the TGF-β pathways, or others like cell therapies or genetic interventions.
Montreal Heart Institute, Université de Montréal, Montreal, QC, Canada.
François
F
Roubille
David
D
Busseuil
Nolwenn
N
Merlet
Ekaterini A
EA
Kritikou
Eric
E
Rhéaume
Jean-Claude
JC
Tardif
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015507:Drugs, Investigational; D005355:Fibrosis / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology*; D012084:Renin-Angiotensin System / Q000187:drug effects
D000959:Antihypertensive Agents; D015507:Drugs, Investigational