Table 1:
Animal and clinical studies assessing cardiac fibrosis therapies.
| Therapeutic Target | Strategy | Year | Model of Fibrosis | Species | Ref |
|---|---|---|---|---|---|
| RAAS | Renin inhibition (aliskiren)* | 2013 | Hyperhomocysteinemia- induced myocardial fibrosis |
Mice | 29 |
| Pro-renin receptor blockade | 2016 | Myocardial infarction | Mice | 38 | |
| ACE inhibition (lisinopril)* | 1991 | Spontaneous hypertension | Rat | 40 | |
| ACE inhibition (trandolapril)* | 1995 | Spontaneous hypertension | Rat | 43 | |
| ACE inhibition (captopril)* | 1997 | Spontaneous hypertension | Rat | 44 | |
| ACE inhibition (lisinopril)* | 2000 | Patients with primary HTN, LV hypertrophy, and LV diastolic dysfunction | Human | 42 | |
| ACE inhibition (perindopril)* | 2006 | HFpEF | Human | 48 | |
| ACE inhibition (captopril)* | 2017 | LPS-induced inflammation | Rat | 45 | |
| ARB (losartan)* | 1997 | Myocardial infarction | Rat | 47 | |
| ARB (valsartan)* | 2002 | Transaortic constriction | Mice | 46 | |
| ARB (candesartan)* | 2003 | HFpEF | Human | 49 | |
| ARB (irbesartan)* | 2008 | HFpEF | Human | 50 | |
| Aldosterone antagonist (spironolactone)* | 1992 | Renovascular hypertension | Rat | 54 | |
| Aldosterone antagonist (spironolactone)* | 1996 | Chronic HF patients | Human | 58 | |
| Aldosterone antagonist (spironolactone)* | 1999 | HFrEF | Human | 59 | |
| Aldosterone antagonist (spironolactone)* | 2014 | HFpEF | Human | 57 | |
| Aldosterone antagonist (spironolactone)* | 2018 | HFpEF | Human | 60 | |
| TGFβ Signaling | TGFβRII plasmid transfection | 2004 | Myocardial infarction | Mice | 73 |
| SM16 (inhibitor of ALK5) | 2014 | Pressure overload | Mice | 72 | |
| GW788388 (inhibitor of ALK5 and TGFpRII) | 2010 | Myocardial infarction | Rats | 79 | |
| GW788388 (inhibitor of ALK5 and TGFpRII) | 2012 | Chagas | Mice | 77 | |
| GW788388 (inhibitor of ALK5 and TGFpRII) | 2017 | Scn5a+/− | Mice | 78 | |
| Pirfenidone | 2002 | DOCA-salt hypertension | Rats | 83 | |
| Pirfenidone | 2010 | Myocardial infarction | Rats | 84 | |
| Pirfenidone | 2013 | Pressure overload | Mice | 85 | |
| Pirfenidone | 2015 | Pressure overload | Mice | 86 | |
| Tranilast | 2004 | DOCA-salt hypertension | Rats | 94 | |
| Tranilast | 2013 | Myocardial infarction | Rats | 95 | |
| Tranilast | 2016 | Viral myocarditis | Mice | 93 | |
| Biomaterials | Hydrogel (alginate) | 2009 | Myocardial infarction | Porcine | 104 |
| Hydrogel (polyester-VEGF) | 2011 | Myocardial infarction | Rats | 121 | |
| Hydrogel (decellularized ECM) | 2012 | Myocardial infarction | Rats | 133 | |
| Hydrogel (alginate-chitosan) | 2014 | Myocardial infarction | Rats | 103 | |
| Hydrogel (gelatin-HGF) | 2014 | Chronic myocarditis | Rats | 111 | |
| Hydrogel (CorMatrix®-ECM) | ongoing | CABG after myocardial infarction | Human | 138 | |
| Hydrogel (VentriGel) | ongoing | STEMI undergoing PCI | Human | 140 | |
| Patch (alginate-neonatal rat CMs) | 2009 | Myocardial infarction | Rats | 120 | |
| Patch (hiPS-CMs) | 2012 | Myocardial infarction | Porcine | 130 | |
| Patch (decellularized ECM) | 2016 | Ischemia-reperfusion | Porcine | 136 | |
| Glue (fibrin-FGF) | 2010 | Myocardial infarction | Canine | 118 | |
| Microspheres | 2006 | Myocardial infarction | Canine | 119 | |
| Self-assembling peptides (skeletal myoblasts-PDGF) | 2008 | Myocardial infarction | Rats | 123 | |
| Self-assembling peptides (PDGF-FGF) | 2011 | Myocardial infarction | Rats | 124 | |
| Scaffold (fibrin-ECs-SMCs) | 2011 | Myocardial infarction | Porcine | 100 | |
| Cell Transplantation | Direct Remuscularization skeletal (myoblasts) | 1993 | Mice | 146 | |
| Direct Remuscularization (BM-MSCs) | 2004 | Myocardial infarction | Human | 145 | |
| Direct Remuscularization | 2005 | Myocardial infarction | Human | 141 | |
| Direct Remuscularization (hematopoietic BM stem cell) | 2006 | Myocardial infarction | Human | 142 | |
| Direct Remuscularization (BM-derived progenitor cells) | 2006 | Myocardial infarction | Human | 143 | |
| Direct Remuscularization (myoblast) | 2008 | Ischemic Cardiomyopathy | Human | 157 | |
| Direct Remuscularization (cardiac stem cell) | 2012 | Ischemic Cardiomyopathy | Human | 210 | |
| Direct Remuscularization (hESC-CMs) | 2014 | Myocardial infarction | Monkey | 154 | |
| Direct Remuscularization (hESC-CMs) | 2014 | Myocardial infarction | Pig | 156 | |
| Direct Remuscularization (hESC-CMs and hESC-CVPs) | 2015 | Myocardial infarction | Rat | 153 | |
| Direct Remuscularization (hESC-CVPs) | 2015 | Severe heart failure | Human | 149 | |
| Direct Remuscularization (hESC-CMs) | 2015 | Myocardial infarction | Rat | 155 | |
| Direct Remuscularization (CD34+ Cell) | 2016 | Refractory Angina | Human | 147 | |
| Direct Remuscularization (myoblast) | 2016 | Myocardial infarction | Monkey | 161 | |
| Stimulation of Endogenous CVPs | 2001 | Myocardial infarction | Mice | 166 | |
| Stimulation of Endogenous CVPs (BM-MSCs) | 2008 | Ischemic heart disease | Human | 168 | |
| Stimulation of Endogenous CVPs (BM-MSCs) | 2009 | Myocardial infarction | Pig | 178 | |
| Stimulation of Endogenous CVPs (BM-MSCs) | 2010 | Myocardial infarction | Pig | 173 | |
| Stimulation of Endogenous CVPs (cardiac stem cell c-kit+) | 2011 | Myocardial infarction | Mice | 174 | |
| Stimulation of Endogenous CVPs (cardiac stem cell c-kit+) | 2012 | Heart failure due to Ischemia | Human | 169 | |
| Stimulation of Endogenous CVPs (BM-MSCs) | 2013 | Myocardial infarction & Ischemic heart disease |
Human | 171 | |
| Stimulation of Endogenous CVPs (cardiosphere-derived cells) | 2013 | Myocardial infarction | Mice | 175 | |
| Stimulation of Endogenous CVPs (MSCs and cardiac progenitor cells) | 2015 | Myocardial infarction | Pig | 176 | |
| Stimulation of Endogenous CVPs | 2017 | Myocardial infarction | Pig | 165 | |
| Direct Reprogramming | GMT (retrovirus/lentivirus) | 2010 | N/A |
In vitro -> in vivo (Mice) |
182 |
| GMT/GMTMM (retrovirus/lentivirus) | 2013 | N/A | in vitro (Human) | 183 | |
| Small molecule cocktail + Oct4 | 2014 | N/A |
In vitro (Mouse) |
196 | |
| Chemical cocktail | 2015 | N/A | In vitro (Mouse) | 197 | |
| GMT (retrovirus) | 2012 | Myocardial infarction | Mice | 184 | |
| GMHT (retrovirus) | 2012 | Myocardial infarction | Mice | 185 | |
| GMHT (retrovirus, polycistronic) | 2012 | Myocardial infarction | Mice | 186 | |
| miRNAs (1, 133, 208, and 499) | 2015 | Myocardial infarction | Mice | 198 | |
| GMT (adenovirus) | 2017 | Myocardial infarction | Rats | 188 | |
| GMT (chimeric AAV) | 2018 | Myocardial infarction | Mice | 192 | |
| GMT (sendai virus) | 2018 | Myocardial infarction | Mice | 194 |
*
currently used clinical therapy