TABLE 2.
Genetic modifications of EC exacerbating cardiac dysfunction.
Genetic Modification | Model | Mechanisms | Modifications of cardiac properties | Type of dysfunction |
---|---|---|---|---|
Lipg KO Nakajima et al. (2013) | TAC 12-week-old male mice | ↘ β-oxidation | ↗ Hypertrophy | Systolic dysfunction |
↘ FS | ||||
↗ NPPA and NPPB | ||||
Pulmonary edema | ||||
EC Tg (NOX2) Murdoch et al. (2014) | ANG2 | ↗ ROS | ↘ LV end-systolic volume | Diastolic dysfunction |
1.1 mg/kg/day | ↗Fibrosis (COL1A1) | ↘ Stroke volume | ||
14 days | ↗Inflammation (CD45+, Mac3+) | ↘ LV end-diastolic dimension and volume | ||
12-week-old male mice | ||||
S1pr1 ECKO Liu et al. (2020) | TAC (1 week after TAM injection) | ↗ Fibrosis | ↗Hypertrophy | Systolic dysfunction |
↘ FS | ||||
↘ EF | ||||
Foxp1 ECKO Liu et al. (2019) | ANG2 | ↗ Fibrosis (COL1A1, COL3A1, TGFβ 1, fibroblast proliferation) | ↗ Hypertrophy | Diastolic dysfunction |
1.44 mg/kg/day | ↗E/e' | |||
14 days | ↗CM size | |||
(1 week after TAM injection) | ||||
Hif1a ECKO Wei et al. (2012) | TAC male mice | ↘ Vascular density | ↘ EF | Systolic dysfunction |
↗ Myocardial hypoxia | ↘ FS | |||
↗ Fibrosis (TGF-β) | ↗ Hypertrophy | |||
Sirt3 ECKO Zeng et al. (2020b) | TAC 7 weeks after | ↘ APLN | ↗ Hypertrophy | Systolic dysfunction |
↘ HIF1a | ↘ EF | |||
↘ GLUT1 | ↘ FS | |||
↘ Glucose uptake |
Lipg, Lipase G; Endothelial Type, NOX2, NADPH Oxidase 2; S1pr1, Sphingosine-1-Phosphate Receptor 1; Foxp1, Forkhead Box P1; Hif1a, Hypoxia Inducible Factor 1 Subunit Alpha; Sirt3, Sirtuin 3; TAC, transverse aortic constriction; TAM, tamoxifen; ANG2, Angiotensin 2; ROS, reactive oxygen species; FS, fractional shortening; EF, ejection fraction; LV, left ventricular.