**Author details**

of HoxD genes has been shown to be temporally regulated as the expression of HoxD10 is maximal 3 days after stimulation with angiogenic factors, whereas the expression of HoxD3 increases after 3 days, indicating that the differentiation and maturation of endothelial cells

uPAR, urokinase receptor; MMP-14, matrix metalloproteinase-14; EhB4, ephrin type-B receptor 4; eNOS, endothelial nitric oxide synthase; VEGFR2, vascular endothelial growth factor receptor 2; Myh10, myosin heavy chain 10; MLL,

Hox genes have been traditionally recognized as genes involved in the embryonic development; however, further research showed that homeobox genes also play a role as master regulators of tissue and organ patterning in adults. These genes can regulate cell differentiation, proliferation, and migration to tissues exposed to constant turnover, such as vasculature,

work alongside with changes in the expression of Hox genes [90].

histone-lysine N-methyltransferase; HUVEC, human umbilical vein endothelial cell.

**Table 1.** Regulation of the Hox genes in vascular cells.

**6. Conclusions**

**Cellular type Hox** 

Human microvasculature endothelial cells

Murine embryonic stem cells

Vascular smooth muscle cells

Vascular smooth muscle cells

Human pulmonary endothelial cells

Human brain endothelial cells

*Anti-angiogenic*

Human endothelial

cells

**genes**

40 Endothelial Dysfunction - Old Concepts and New Challenges

**Period of expression**

HoxA13 Postnatal

Angioblasts (rat) HoxB5 Neovascularization VEGFR2 + Endothelial cell

HUVECs HoxD3 Neovascularization Collagen1A1 + Adhesion and

HUVECs HoxA5 Postnatally VEGFR2 – Endothelial cell

neovascularization

**Target gene Regulation Functions Reference**

Integrin-α + [78]

EphA4 + Organización

EphA7 +

Prx1 Late embryogenesis TN-C + Proliferation of

Prx2 Late embryogenesis TN-C + Proliferation of

Hhex Vascular insult Myh10 + Plasticity smooth

Meox2 Postnatally MLL77 — Endothelial cell

HoxD10 Postnatally Integrin-α — Endothelial cell

activation

migration of endothelial cells

células endoteliales y formación de vasos

smooth muscle

smooth muscle

muscle cells

apoptosis

activation

migration

migration

cells

cells

α-Actin + [65]

Ephrin A1 – Endothelial cell

[66]

[77]

[54]

[85]

[85]

[84]

[66]

[86]

[87]

[53]

Estefanía Nova-Lampeti1 , Valeria Aguilera<sup>1</sup> , Katherine Oporto<sup>1</sup> , Paula Guzmán<sup>1</sup> , Valeska Ormazábal<sup>2</sup> , Felipe Zúñiga1 , Carlos Escudero3,4 and Claudio Aguayo1,4\*

\*Address all correspondence to: caguayo@udec.cl

1 Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepcion, Chile

2 Department of Pharmacology, Faculty of Biological Sciences, University of Concepcion, Concepcion, Chile

3 Vascular Physiology Laboratory, Group of Investigation in Tumor Angiogenesis (GIANT), Department of Basic Sciences, University of Bio-Bio, Chillan, Chile

4 Group of Research and Innovation in Vascular Health (GRIVAS Health), Chillan, Chile
