Endoglin: a critical mediator of cardiovascular health

Figures & data

Figure 1 Endoglin signaling in endothelium.

Notes: Under normal conditions, endoglin promotes transforming growth factor beta-1 signaling via both ALK-1 and ALK-5, which balances endothelial quiescence and proliferation, thereby promoting vascular homeostasis. When endoglin expression is reduced, as in hereditary hemorrhagic telangiectasia 1, signaling via ALK-1 is attenuated, while ALK-5 activity is increased, thereby promoting arrest of endothelial proliferation and impairing vascular homeostasis.
Abbreviation: ALK, activin receptor-like kinase; P, phospho.

Figure 2 Circulating angiogenic peptides in pre-eclampsia.

Notes: Soluble endoglin is released by ectodomain cleavage of membrane-associated endoglin, thereby disrupting TGFβ1 signaling. Soluble Flt1 is generated by either ectodomain cleavage of the VEGF receptor type I or alternative splicing of FLT-1 pre-mRNA and interferes with VEGF signaling.
Abbreviations: TGFβ1, transforming growth factor beta-1; PIGF, placental growth factor; VEGF, vascular endothelial growth factor; sEng, soluble endoglin; mRNA, messenger RNA.

Figure 3 Canonical and noncanonical transforming growth factor beta-1/endoglin signaling in fibrosis.

Notes: On binding of transforming growth factor beta-1 to a heteromeric complex of receptors including type I, type II, and endoglin, downstream signaling via Smad-dependent or Smad-independent pathways occurs. Smad-3 promotes collagen synthesis by activating transforming growth factor beta-1 activated kinase or CTGF. Smad-3 can also directly activate collagen synthesis by binding a Smad-binding element within the collagen promoter. Noncanonical signaling can stimulate collagen synthesis via several mitogen-activated protein kinases including ERK, JNK, or p38 kinase.
Abbreviations: CTGF, connective tissue growth factor; ERK, extracellular regulated kinase; JNK, jun-n-terminal kinase; Eng, endoglin; MAPK, mitogen-activated protein kinase.

Figure 4 Functional role of endoglin in cardiac fibrosis.

Notes: In heart failure, increased ventricular pressure overload stimulates TGFβ1 expression. In mice with normal endoglin expression (Eng^+/+), endoglin promotes TGFβ1-induced type I collagen synthesis and cardiac fibrosis. Reduced endoglin expression in Eng^+/− mice attenuates TGFβ1-induced pSmad-2/3, type I collagen expression, and cardiac fibrosis.
Abbreviation: TGFβ1, transforming growth factor beta-1.