Table 1.
Summary of vascular effects in mouse models of E2 and pharmacological ligands.
| Mouse Models | Names | Description | Effect on Vascular Protection | Reference |
|---|---|---|---|---|
| ERβ- null | ERβ-KO | Global deletion of ERβ by deleting Exon2 | Preserved E2-induced acceleration of re-endothelialization, Preservation of arterial flow-mediated remodeling |
[43,56,68] |
| ERα- null | ERα-KO | Global deletion of ERα by deleting Exon2 | Loss of endothelial NO production, Loss of E2-induced acceleration of re-endothelialization, Absence of E2-induced atheroprotection, Absence of arterial flow-mediated remodeling, Absence of angiotensin II-induced hypertension, Absence of E2-induced prevention of lymphedema |
[15,43,56,59,68,69] |
| ERα-Neo KO | ERα-KO | Insertion Neo Cassette in exon 1 | Preserved endothelial NO production | [59] |
| ERα- AF1 mutant | ERα-AF10 | Deletion of -1-148)aa AF1 domain | Preserved endothelial NO production, Preserved E2-induced acceleration of re-endothelialization following perivascular electric injury, Preserved E2-induced atheroprotection, Abrogation of the neointimal hyperplasia protection induced by E2 |
[20,22] |
| ERα- AF2 mutant (loss of nuclear signaling) | ERα-AF20 | Deletion of AF2 domain | Loss of endothelial NO production, Loss of E2-induced acceleration of re-endothelialization following perivascular electric injury, Absence of E2-induced atheroprotection, Absence of angiotensin II-induced hypertension |
[21,69] |
| ERα- AF2 mutant | AF2ERKI | Mutation of L L543A, L544A in helix 12 | Not determined | [70] |
| Loss of membrane signaling | C451A-ERα, NOER | Mutation of palmitoylation site (C451A) | Loss of endothelial NO production, Loss of E2-induced acceleration of re-endothelialization following perivascular electric injury, Preserved E2-induced atheroprotection, angiotensin II-induced hypertension and flow-mediated arteriolar remodeling |
[64,69,71,72] |
| Inactivation of extra-nuclear signaling | DPM mice | Overexpression of a peptide preventing striatin interaction | Loss of E2-induced protection against medial hyperplasia following wire carotid injury | [67] |
| Inactivation of ERα on hematopoietic and lymphatic/ endothelial cells | Tie2-CRE- ERαL2L2 | Expression of Cre recombinase under Tie2-promoter | Loss of E2-induced acceleration of re-endothelialization, Absence of E2-induced atheroprotection, Absence of arterial flow-mediated remodeling on a model of ligation of 2 mesenteric arteries, Preserved protective E2 effect against neointimal hyperplasia after wire femoral injury, Absence of E2-induced prevention of lymphedema, Lymphatic leakage and hyperdilated lymphatic capillaries |
[15,22,62,68,73] |
| Inactivation of ERα on endothelial cells | VE-Cad-CRE- ERαL2L2 | Expression of Cre recombinase under VE-Cad promoter | Decrease of vascular thickness in WD-fed females and males fed evaluated by pulse wave velocity Doppler ultrasound, Preserved mesenteric remodeling in WD-fed females, Lymphatic leakage and dilated lymphatic capillaries |
[74,75] |
| Selective activation of Membrane ERα | EDC | (estrogen-dendrimer conjugate) | Activation of endothelial NO production, Acceleration of re-endothelialization following perivascular electric injury, Protection on medial hyperplasia after wire carotid injury, No protection against neointimal hyperplasia after wire femoral injury, No atheroprotection |
[22,63,72,76] |
| Selective activation of Membrane ERα | PaPE | Pathway Preferential Estrogens | Acceleration of re-endothelialization following perivascular electric injury, Activation of eNOS activation, Protection against stroke on a mice model of middle cerebral artery occlusion, No atheroprotection |
[24,72,77] |
| Selective activation of Nuclear ERα | E4 | Estetrol (Fetal estrogen) | No acceleration of re-endothelialization, Preserved atheroprotection, angiotensin II-induced hypertension and flow-mediated arteriolar remodeling on a model of ligation of 2 mesenteric arteries, Protection against neointimal hyperplasia after wire femoral injury |
[22,25,72,78] |
| Selective modulation of ERα (agonist AF-1) | TAM | Tamoxifen | No acceleration of re-endothelialization after electric carotid injury, Protection against atheroprotection Protection against neointimal hyperplasia after wire femoral injury, Absence of protection against lymphedema |
[22,61,79] |
NOER: Nuclear only ER; DPM:Disrupting Peptide Mouse; WD:Western diet.