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. 2022 Jul 8;13:906272. doi: 10.3389/fphys.2022.906272

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.