Table 1.
Characteristics of mouse models of CAVD.
| Model | Insult*, duration, (treatment) | Total chol† | Results, (treatment) | Study |
|---|---|---|---|---|
| Mouse | ||||
| WT C57BL/6J | 58.7% fat, <0.1% cholesterol, 4 mo | 166 ± 4 | ↑T, TV, M, Tc, C; ↓OA | Drolet et al. 2006 [34] |
| WT C57BL/6J | 9% fat (w/w), 1.25% chol, 0.5% cholic acid, 15–22 wk | — | ↑M on high-shear ventricular face, no Δ in L or LPR | Mehrabian et al. 1991 [35] |
| Ldlr−/− | 42% fat, 0.2% chol., 4 mo | 1040 ± 37 | ↑mineral deposition reported | Towler et al. 1998 [36] |
| Ldlr−/− | 42% fat, 0.15% chol., 4 mo | 1958 ± 235 | ↑M, SO, My, O, C | Matsumoto et al. 2010 [37] |
| Ldlr−/−;Apob100/100 | normal diet, 20 mo | 271 ± 12 | ↑LV hypertrophy, C, SO; ↓OA | Weiss et al. 2006 [38] |
| Ldlr−/−;Apob100/100/Mttpfl/fl/Mx1-Cre+/+, “Reversa” | 42% fat, 0.25% chol., 6–12 mo, (Reversal) | 997 ± 87 | ↑L, M, My, PFS, Col, PCS, SO, C; ↓OA, (↓ all but Col; ↓TC) | Miller et al. 2009 [39] |
| “Reversa”, as above | 42% fat, 0.25% chol., 14 mo, (Reversal) | 571 ± 54 | ↑PFS, PCS, SO, C; ↓OA, (↓ all but PFS, SO; does not ↑OA; ↓TC) | Miller et al. 2010 [40] |
| Apoe−/− | Normal diet, 30 mo | — | ↑TV, M, Tc, My, O, C | Tanaka et al. 2005 [41] |
| Apoe−/− | 42% fat, 0.15% chol., 4 & 16 mo | — | ↑macrophage-targeted NIRF signal | Aikawa et al. 2007 [42] |
| Apoe−/− | 42% fat, 0.2% chol., 5 mo | 588 ± 47 | ↑T, M, My, O, MMP-2/9, microC, ALP, cathepsinB/K, activated VECs | Aikawa et al. 2007 [43] |
| Apoe−/− | 42% fat, 0.2% chol., 125 μg/day leptin, 2 mo | 4709 ± 247 | ↑O, C, ALP | Zeadin et al. 2009 [44] |
| Apoe−/− | Normal diet, 2.5 mg/kg/day acrolein, 8 wk | 564 ± 17 | ↑M, L, activated VECs, TC, VLDL, PF4; no ↑My or SO | Srivastava et al. 2011 [45] |
| Apoe−/−;Ctss−/− | 42% fat, 0.2% chol., 5/6 nephrectomy, 5 mo | 660 ± 25 | ↓M, C, O, elastolytic activity, elastin fragment versus Ctss+/+ | Aikawa et al. 2009 [46] |
| Apoe−/− | Normal diet, 5/6 nephrectomy, 6 mo | 397 ± 25 | ↑M, microC, osteoporosis | Hjortnaes et al. 2010 [47] |
| Mgp−/− | Normal diet, 2-3 wk | n/a | ↑valve calcification reported | Luo et al. 1997 [48] |
| Fibulin4−/− | Normal diet, 4-5 mo | n/a | ↑T, functional impairment, PFS, PCS, immune response gene | Hanada et al. 2007 [49] |
| Eln+/− | Normal diet, 1 wk–17 mo | n/a | ↑proliferation of VICs, regurgitation | Hinton et al. 2010 [50] |
| Notch1+/− | 42% fat, 0.2% chol., 10 mo | — | ↑C by 5x, ALP; no bicuspid aortic valves | Nigam and Srivastava 2009 [51] |
| RBPJk+/− | 1.25% chol., 0.5% sodium cholate, 5 IU VitD3, 4 mo | ~200 | ↑T, M, Col, TV, PFS, PCS, C; ↓FS and EF; no bicuspid aortic valves | Nus et al. 2011 [52] |
| Postn−/− | Normal diet, 10 mo | n/a | ↑bicuspid-like aortic valves, PCS, C | Tkatchenko et al. 2009 [53] |
| Postn−/− | 57% fat, 4 mo | ~145 | ↓T, M, My, annular fibrosis, MMP-2/13 versus WT on HF diet | Hakuno et al. 2010 [54] |
| ChmI−/− | Normal diet, 21–24 mo | n/a | ↑T, L, C, AVA, VEGF-A, angiogenesis | Yoshioka et al. 2006 [55] |
| Nos3−/− (eNOS) | Normal diet, 25–30 g | n/a | ~50% bicuspid aortic valve incidence | Lee et al. 2000 [56] |
| Madh6−/− | Normal diet, 6 wk | n/a | ↑valve hyperplasia, aortic ossification | Galvin et al. 2000 [57] |
| persistent Twist1 | Normal diet, 1 wk & 6.5 mo | n/a | ↑T, Col2a1, periostin, MMP-2/13; ↓OA | Chakraborty et al. 2010 [58] |
| hypomorphic Egfr | Normal diet, 1 wk–12 mo | n/a | ↑M, C, O, congenitally enlarged valves | Barrick et al. 2009 [59] |
| Il1rn−/− | Normal diet, 4–40 wk | ~90 | ↑T, M, My, C, TV, TNF-α | Isoda et al. 2010 [60] |
*% fat: % kcal from fat unless otherwise noted.
†mg/dL. Normal total cholesterol ranges: human: 197 ± 23 mg/dL [61], mouse: 90–110 mg/dL, rabbit: 30–60 mg/dL, swine: 60–75 mg/dL.
↑: increased compared to control, ↓: decreased compared to control, ALP: alkaline phosphatase activity, AVA: aortic valve area, C: calcification, Col: collagen, EF: ejection fraction, FS: fractional shortening, HF: high fat, L: lipid deposition, LPR: lipoprotein infiltration, LV: left ventricle, M: macrophage, My: myofibroblast, n/a: not applicable, OA: opening area, O: osteoblast, PCS: procalcific signalling, PFS: profibrotic signalling, PF4: platelet factor 4, SO: superoxides, T: thickness, Tc: T-cell, TC: total cholesterol, TV: transvalvular velocity, VEC: valve endothelial cells, VIC: valve interstitial cells, VLDL: very low-density lipoprotein, and WT: wild type.