| Compound | Study summary | [Ref.] | |
| Protective effects of selective or pan-MMP inhibition | |||
| MCT-induced PH | |||
| Bosentan (ETA and ETB) | Bosentan attenuated MCT-induced PH and increased gene expression of MMP-2 and TIMP-1 | [104] | |
| Fluoxetine (serotonin re-uptake inhibitor) | Fluoxetine significantly suppressed MCT-induced increase of MMP-2, MMP-9, TIMP-1 and TIMP-2 expression in a dose-dependent manner, associated arterial muscularisation and inhibited MCT-induced PH | [105] | |
| Fluoxetine | Fluoxetine significantly inhibited MCT-induced increases in the expression of OPN, MIP-1β and MMP-2/TIMP-2 | [106] | |
| Captopril (ACEi) and losartan (AT1R antagonist) | Captopril (ACEi) and losartan (AT1 receptor antagonist) attenuated the increased expression of MMP-2, MMP-9, TIMP-1, pulmonary vascular remodelling and PAH induced by pneumonectomy plus MCT injection in rats | [115] | |
| SD-208 (Alk5 inhibitor) | Orally active Alk5 inhibitor, SD-208-inhibited TGF-β signalling and MCT-induced increase in MMP-2 and MMP-9 expression and attenuated the development of PH | [107] | |
| Amlodipine (Ca2+ channel blocker) | Amlodipine following MCT markedly inhibited PH and MCT-induced increase in MMP-2 and pro-inflammatory cytokines in the lung | [133] | |
| STI571 (PDGFR inhibitor) | PDGFR inhibitor STI571 strongly attenuated the upregulation of MMP-2 and MMP-9 expression and activity in MCT-induced PH | [109] | |
| Tolafentrine (combined PDE3/4 inhibitor) | Inhalation of combined PDE3/4 inhibitor reversed the upregulation of MMPs, PASMC migration and the fully established PH in response to MCT in rats | [100] | |
| Iloprost (prostacyclin analogue) | Inhalation of iloprost reversed PAH and suppressed the MCT-induced increase in MMP-2 and MMP-9 activities and TN-C expression | [108] | |
| Iloprost and tolafentrine | Combined administration of iloprost and a dual-selective PDE3/4 inhibitor reversed the development of MCT-induced PH and the time-dependent increase in MMP-2 and MMP-9 expression and associated gelatinolytic activity in pulmonary arteries in response to MCT | [101] | |
| TIMP-1 gene transfer | In vivo MMP inhibition in lungs by human TIMP-1 gene transfer was associated with significant reduction in pulmonary vascular remodelling in the model of MCT-induced PH | [6] | |
| GM-6001 (MMP inhibitor) and serine elastase inhibitor | Both MMP inhibitor GM-6001 and serine elastase inhibitor (α1-PI) in organ culture induced regression of vascular disease by reduction in serine elastase and MMP-2 activity | [111] | |
| Hypoxia-induced PH | |||
| Batimastat (synthetic MMP inhibitor) | Batimastat treatment markedly attenuates the development of hypoxic PH by inhibiting the increase in collagenolytic activity in peripheral pulmonary arteries | [113] | |
| Selective or pan-MMP inhibition leads to the exacerbation of PH | |||
| Hypoxia-induced PH | |||
| Doxycycline and human TIMP-1 gene transfer | MMP inhibition by doxycycline treatment and by overexpression of human TIMP-1 in the lungs of rats subjected to chronic hypoxia aggravated vascular remodelling and PH | [134] |
MCT: monocrotaline; ET: endothelin; ACEi: angiotensin-converting enzyme inhibitor; AT1R: angiotensin type 1 receptor; PDGFR: platelet-derived growth factor receptor; PDE: phosphodiesterase; TIMP: tissue inhibitor of metalloproteinase; AT1: angiotensin II type 1; OPN: osteopontin; MIP: macrophage inflammatory protein; PAH: pulmonary arterial hypertension; TGF: transforming growth factor; TN-C: tenascin-C; PASMC: pulmonary artery smooth muscle cell; α1-PI: α1-proteinase inhibitor.