Table 2.
Therapies targeting oxidative stress pathways in animal and in vitro models of aortic stenosis. BMP2 = bone morphogenetic protein 2; DPP-4 = dipeptidyl peptidase-4; DRP1 = dynamin-related protein 1; Lp(a) = lipoprotein(a); NADPH = nicotinamide adenine dinucleotide phosphate; NOS = nitric oxide synthase; oxLDL = oxidesed low density lipoproteins; oxPL = oxidised phospholipids; VIC = valvular interstitial cells.
| First Author [Ref] | Year | Study Type | Key Findings |
|---|---|---|---|
| Bosse K 50 | 2013 | In vitro - porcine VICs | Inhibition of NOS increases calcification |
| Choi B 46 | 2017 | Mouse model - eNOS -/- Rabbit model with cholesterol-enriched diet |
DPP-4 inhibition reduced aortic valve calcification Sitagliptin administration in a rabbit model with calcific aortic valve disease improved the rate of change in aortic valve area, transaortic peak velocity, and maximal and mean pressure gradients |
| Liberman M 54 | 2008 | Rabbit model with cholesterol-enriched diet | In vivo treatment with lipolic acid, which aids the metabolism of hydrogen peroxide, decreases aortic valve calcification |
| Liu H 57 | 2020 | In vitro - porcine VICs | Celastrol, which inhibits NADPH oxidase 2, significantly reduced calcification in porcine VICs |
| Rabbit model with cholesterol-enriched diet | Celastrol, which inhibits NADPH oxidase 2, reduced aortic valve ROS production, fibrosis, calcification and AS severity | ||
| Nadlonek NA 123 | 2013 | In vitro - human VICs | oxLDLs increased the expression of phosphate inorganic transporter 1 and BMP2, with resultant calcium and phosphate deposition. Inhibition of phosphate inorganic transporter 1 with phosphonoformate hexahydrate acid prevented oxLDL-induced BMP2 expression. |
| Rajamannan NM 30 | 2005 | Rabbit model with chronic hypercholesterolaemia | Atorvastatin inhibits bone mineralisation in the aortic valve by increasing the protein expression and functional activity of endothelial NOS |
| Ratazzi M 44 | 2020 | In vitro - bovine VICs stimulated to acquire a pro-calcific phenotype with endotoxin | L-Arginine, a precursor of NO, prevents osteogenic differentiation and reduces calcification |
| Rogers MA 58 | 2017 | In vitro - human VICs | DRP1 inhibition attenuates VIC calcification |
| Zheng KH 41 | 2019 | In vitro - human VICs incubated in an osteogenic medium with Lp(a) and OxPL | Incubation with the E06 monoclonal antibody against OxPL reduced osteogenic differentiation of VICs |