Table 1.
Vascular epidermal growth factor receptor pathophysiology
| Model | Intervention | Outcome and intermediate | Reference(s) |
|---|---|---|---|
| Hypertension (AngII infusion or SHR) | EGFR antisense | Reduced hypertension ERK1/2 | 55, 56 |
| Hypertension/renal injury (5/6 nephrectomy) | PKI-166 | Reduced progression of hypertension; partially restored contractile response | 59 |
| Hypertension/vascular remodeling (AngII infusion) | Erlotinib | Reduced vascular remodeling; did not reduce hypertension; reduced ADAM17 and ER stress | 61 |
| Hypertension/vascular remodeling (AngII infusion) | AG1478 waved-2 mouse | Reduced cerebral arteriole hypertrophy; did not reduce hypertension | 63 |
| Hypertension/renal dysfunction (L-NAME treatment and removal) | Gefitinib | Restored functional endothelial cells; did not reduce hypertension | 89 |
| Restenosis (balloon angioplasty) | Monoclonal antibody targeting EGFR | Inhibited medial smooth muscle cell proliferation and intimal hyperplasia | 66 |
| Restenosis (balloon angioplasty) | ADAM17 dominant-negative adenovirus | Reduced intimal hyperplasia EGFR inhibition | 68 |
| Vascular remodeling (partial ligation) | HB-EGF−/− mouse | Inhibited medial smooth muscle cell proliferation and intimal hyperplasia | 69 |
| Abdominal aortic aneurysm (AngII with BAPN infusion) | Erllotinib | Reduced abdominal aorta diameter and increased survival; decreased ADAM17, MMP2, IL-6, and ER stress markers | 76 |
| Endothelial dysfunction (aldosterone/salt/nephrectomy) | Waved-2 mouse | Restored endothelial dysfunction and inhibited AngII-induced contraction; did not affect vascular remodeling | 90 |
| Endothelial dysfunction (STZ-induced type 1 diabetes) | AG1478 | Restored endothelial function and eNOS expression; reduced ER stress | 91 |
| Endothelial dysfunction (db−/− mice) | AG1478 | Restored endothelial function and eNOS expression | 92 |
| Neovascularization (oxygen-induced retinopathy) | Erlotinib TIMP-3−/− mouse | Reduced neovascularization | 93 |
| Neovascularization (oxygen-induced retinopathy) | EC ADAM17 KO mouse | Reduced neovascularization and HB-EGF production | 94 |
Abbreviations: ADAM, a disintegrin and metalloprotease; AngII, angiotensin II; BAPN, beta aminopropionitrile; EC, endothelial cell; EGFR, epidermal growth factor receptor; eNOS, endothelial nitric oxide synthase; ER, endoplasmic reticulum; ERK, extracellular signal-regulated kinase; HB-EGF, heparin-binding epidermal growth factor–like growth factor; IL-6, interleukin 6; KO, knockout; SHR, spontaneously hypertensive rat; STZ, streptozotocin; TIMP-3, tissue inhibitor of metalloprotease-3.