TABLE 1.
Misexpression of TGFβ signaling components lead to (cardio)vascular abnormalities.
| Gene | Human disease | Animal model | Reference |
|---|---|---|---|
| Ligands | |||
| TGFβ1 | Camurati-Engelmann disease |
KO: embryonic lethal with vascular defects or postnatal lethality from autoimmune disease. | 13-16 |
| TGFβ2 | Kawasaki disease | KO: aortic arch defects, cardiac septal defects, perinatal lethality. | 17,18 |
| TGFβ3 | unknown | KO: cleft palate, delayed lung maturation, die shortly after birth. | 19,20 |
| Receptors | |||
| TβRII | MFS2, LDS | KO: embryonic lethal, vascular defects | 21,136 |
| TβRI/ALK5 | LDS | KO: embryonic lethal, angiogenesis defects | 22,145,146 |
| ALK1 | HHT | KO: embryonic lethal, reduced VSMC differentiation, dilated vessels, AVMs | 23,24 |
| BMPRII | PAH | KO: pre-angiogenesis lethality Transgenic BMPR2-mutant allele: pulmonary hypertension |
25-27 |
| Accessory receptors | |||
| ENG (endoglin) | HHT | KO: embryonic lethal due to vascular defects, reduced vSMC differentiation, heart defects. Het: vascular lesions similar to HHT. |
28-30 |
| Soluble Endoglin TGFBR3 (betaglycan) |
Pre-eclampsia Familial intracranial aneurysm |
KO: poorly formed cardiac septa, incomplete compaction of ventricular walls |
51 31 |
| Smads | |||
| Smad1 | Unknown | KO: embryonic lethal due to defects in chorion-allantoic circulation | 32 |
| Smad3 | Aortic aneurysm-osteoarthritis | 33-37 | |
| Smad4 | JP and HHT | KO: embryonic lethal | 38-40 |
| Smad5 | Unknown | KO: embryonic lethal due to angiogenesis defects | 41-43 |
| Smad6 | Unknown | KO: heart abnormalities, aortic ossification and elevated blood pressure | 44 |
| Smad7 | Unknown | KO: embryonic lethal due to cardiovascular defects | 45 |
| Smad8 | PAH | Defective pulmonary vascular remodeling | 46 |
Abbreviations: KO, knockout; Het, heterozygous; AVMs, arteriovenous malformations; LDS, Loeys-Dietz syndrome; MFS2, Marfan syndrome type 2; HHT, hereditary haemorrhagic telangiectasia; PAH, pulmonary arterial hypertension; JP, Juvenile polyposis; VSMC, vascular smooth muscle cell.