**Author details**

quantitative and molecular studies were undertaken to test the potentiality of hypobaric hypoxia to induce angiogenesis, to detect possible differences in vascular density in pulmonary hypertensive chickens and to correlate these findings with mRNA expression of some key genes for angiogenesis. Under hypobaric hypoxic conditions (altitude 2638 m above sea level, (oxygen tension: approximately 111 mmHg), both, healthy and pulmonary hypertensive birds, had more blood vessels with diameter ranges between >100-200, >200-300 and >300-500 µm, as compared to healthy chickens maintained under relative, normobaric, normoxic conditions (460 meters above sea level (oxygen tension: approximately 152 mmHg). However, the opposite was encountered when comparing values obtained for blood vessels within the ≥50-100 µm range. Coincident with this result, decreased expression of hepatocyte growth factor (HGF), HIF-2α, VEGF, Flk-1, and HGFR genes was encountered in the lung of chickens exposed to hypoxia. The same mRNA expression pattern did not show coincidence with observations for blood vessels within the range of 100-500 µm (Areiza et al., 2011, 2012).

It is interesting that the mRNA expression of various genes compromised in both, angiogenesis and vascular remodeling, varies in pulmonary hypertensive (susceptible chickens) versus nonpulmonary hypertensive chickens, which indicates different degrees of resistance or suscept‐ ibility to hypobaric hypoxia (Gómez et al, 2007, 2008; Areiza et al., 2012). This coincidence reinforces the idea that among all the known compensatory mechanisms for low pO2 in the

Promoting angiogenesis, vasculogenesis, or arteriogenesis could represent a possible palliative treatment in individuals chronically exposed to hypobaric hypoxia. It is clear that it would be useful to establish some characteristics of vascular development in the lung of susceptible individuals subjected to chronic hypoxia, in order to design long term treatments, such as vascular neo-formation enhancement. In this context, it is desirable to further investigate the

Again, mesodermal derivatives particularly bone marrow cells, the endothelium, and fibro‐ blasts, act in two different but possibly complementary ways, as a response to hypoxia: the remodeling process and pulmonary vascular neo-formation. However, as has been presently highlighted, some results are controversial, which could not be currently explained, since there is not enough information on the vascular development in the lung, as a result of hypoxic exposure of susceptible and non-susceptible individuals, which would allow for the under‐ standing of the molecular framework of angiogenesis at different stages of development and

Angiogenesis is a distinct mechanism to compensate for the hypoxic conditions within the alveoli (or respiratory capillaries in birds). However, addition of new blood vessels to the lung as a compensatory mechanism, might be a time-dependent process, as it occurs in the placenta, where distinct factors intervene at different times during gestation (Hamilton et al., 1995; Athanassiades and Lala, 1998; Matsumoto et al., 2002; Wulff et al., 2002), and further studies

airways and hypoxemia, angiogenesis is one of them, but it might be a long term one.

**5. Final remarks**

108 Pulmonary Hypertension

chronology of angiogenesis in the hypoxic lung.

possibly, the correspondent genes involved.

Aureliano Hernández\* and Rafael A. Areiza

\*Address all correspondence to: ahernandezv@unal.edu.co

Facultad de Medicina Veterinaria y de Zootecnia, Universidad Nacional de Colombia, Bogotá, Colombia
