TABLE 5.
Genetic modifications of EC properties that protect from developing cardiac dysfunction.
| Model | Mechanism? | Cardiac phenotype | ||
|---|---|---|---|---|
| Nr3c2 ECKO Rickard et al. (2014) | DOC salt mice | ↘ Inflammation (MΦ, CCR5, NOS2, PAI-1 | ND | |
| ↘ Fibrosis (CTGF) | ||||
| ↔ PA | ||||
| Nr3c2 ECKO Jia et al. (2015) | 4-months HFD (45% kCal from fat) mice | ↘ Fibrosis (TGFβ, COL1A1, FN) | ↘ Diastolic relaxation time | ↗ Diastolic function |
| ↘ Inflammation (M1 MΦ) | ↘ IVRT | |||
| ↘ ROS (peroxynitrite) | ↗ E'/A | |||
| Scnn1a ECKOSowers et al. (2020) | 3-months HFD (45% kCal from fat) mice | ↔ Fibrosis | ↗ e’/a’ | ↗ Diastolic function |
| ↘ Oxidative stress | ↘ E/e’ | |||
| (NRF2) | ↘ MPI | |||
| ↘ CM stiffness | ||||
| ↔ Hypertrophy | ||||
| Icam-1 KO Salvador et al. (2016) | TAC mice | ↘ Fibrosis | ↘ Hypertrophy | ↗ Diastolic and systolic function |
| (TGFβ, COL1A1) | ↘ EDP | |||
| ↘ Inflammation | ↘ dP/dt min | |||
| (CD45+, CD3+, CD4+, and Ly6Ghigh) | ↗ FS | |||
| ↘ dP/dt max | ||||
| EC Tg (FOXP1) Liu et al. (2019), 1 | ANG2 mice | ↘ Fibrosis (SMA, COL1A1, COL3A1, VIM) | ↘ Hypertrophy | ↗ Diastolic function |
| ↔ PA | ↘ E/e’ | |||
| Ets1 ECKO Xu et al., (2019) | ANG2 mice | ↔ PA | ↘ Hypertrophy | ND |
| ↘ Fibrosis (TGFβ, COL1A1, COL3A1, FN, CTGF, SMA,FSP1) | ↘ NPPA, NPPB | Systolic function | ||
| ↘ MYH7 | not affected | |||
| ↔ FE | ||||
| Ptpn1 ECKO Gogiraju et al. (2016) | TAC mice | ↗ Capillary density | ↗ FS | ↗ Systolic function |
| ↗ Perfusion | ↘ Hypertrophy | ↗ Survival at 20 weeks | ||
| ↘ Hypoxia | ↘ Lung weight | |||
| ↗ KDR signaling | ||||
| ↘ Fibrosis (TGFβ, αSMA, COL3A1) | ||||
| ↘ Oxidative stress (NOX4) | ||||
| Tp53 ECKO Gogiraju et al. (2015) | TAC female mice | ↗ Capillary density | ↗ FS | ↗ Systolic function |
| ↘ Apoptosis (Caspase 3) | ↘ Hypertrophy | ↗ Survival at 24h | ||
| ↘ Hypoxia (CAIX) | ↘ CM size | |||
| ↔ EC dependent vasodilation | ||||
| ↘ Fibrosis (FSP1, COL1A1) | ||||
| Lepr ECKO Gogiraju et al. (2019) | TAC mice | ↗ Capillary density | ↗ FS | ↗ Systolic function |
| ↘ EC apoptosis | ↘ Hypertrophy | |||
| ↗ mTOR-dependent autophagy | ↘ NPPB | |||
| ↘ Fibrosis | ↗ MYH6/MYH7 ratio | |||
| ↘ VCAM-1 | ||||
| ↘ Inflammation (CD45) | ||||
| ↘ Oxidative stress (DHE) | ||||
| Adk ECKO Davila et al. (2020) | TAC mice | ↗ EC dependent vaso dilation | ↗ EF (+/-) | NS |
| ↘ CM size | ||||
| ↔ Hypertrophy | ||||
| Capns1 ECKO Sun et al. (2020b) | Isoproterenol (5 mg/kg) S.C., 1 dose 1 week-post mice | ↘ Fibrosis | ↘ CM size | Improved cardiac remodeling |
Nr3c2, Nuclear Receptor Subfamily 3 Group C Member 2; ECKO, endothelial cell specific knock out; ND, not determined; Scnn1a, Sodium Channel Epithelial 1 Subunit Alpha; Icam-1, Intracellular Cell Adhesion Molecule 1; FOXP1, Forkhead Box P1; Ets1, ETS Proto-Oncogene 1; Transcription Factor, Ptpn1, Protein Tyrosine Phosphatase Non-Receptor Type 1; Tp53, Tumor Protein P53; Lepr, Leptin receptor; Adk, Adenosine Kinase; Capns1, Calpain Small Subunit 1; DOC, deoxycorticosterone; HFD, High fat diet; MΦ, macrophages; TAC, transverse aortic constriction; ANG2, Angiotensin 2; IVRT, isovolumic relaxation time; MPI, myocardial performance index; CM, cardiomyocyte; EDP, end diastolic pressure; EF, ejection Fraction; FS, Fractional shortening; DHE, 2-hydroxy-ethidium.