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Alfonso Calvo Gonzalez, researcher of Cima and professor of Cell Biology and Histology of the University

Key cellular mechanisms for new treatments development

Tue, 08 Oct 2019 17:48:00 +0000 Published in Navarra Newspaper

That oxygen is essential for cellular respiration and metabolism has long been known. The novelty of the discoveries of the researchers W.G. Kaelin, P.J. Ratcliffe and G.L. Semenza, recent winners of the award Nobel Prize in Medicine and Physiology, lies in the identification of sensors by which cells detect oxygen deficiency. The alteration of this system is directly or indirectly implicated in numerous diseases, such as diabetes, anemia, cancer, stroke, myocardial infarction, etc.

When certain pathological conditions lead to a decrease in the oxygen needed by tissues, known as hypoxia, cellular sensors trigger an alarm system aimed at counteracting this effect. One of the sensors core topic is hypoxia-inducible factor-1 (HIF-1), whose activity leads the cells to produce proangiogenic factors, responsible for increasing the vascularization of the tissue and, therefore, a greater supply of oxygen from the red blood cells circulating in the vessels. One of these factors, VEGF, or vascular endothelial growth factor, has a strong provascularizing effect. Another factor core topic is erythropoietin, a hormone produced mainly in the kidney, whose effect is to produce a greater number of red blood cells issue and thus increase the hematocrit.

Oxygen sensor failure particularly affects the cardiovascular system, which supplies all body tissues, so a good understanding of the normal and pathological mechanism of the sensors is core topic to try to remedy it.

The discoveries of the award winners have enabled the development of new targeted drugs, either to enhance tissue vascularization when more oxygen is required, as in myocardial infarction, or to stop pathological vascularization, as in cancer or diabetic retinopathy. An example of an anti-angiogenic drug widely used in these diseases is bevacizumab, which prevents exacerbated and pathological growth of blood vessels, without affecting the normal vasculature. There is currently an enormous pharmacological arsenal capable of modulating oxygen supply, either by favoring normal growth in ischemic (poorly irrigated) tissues, or by inhibiting pathological growth.

Therefore, this year's award Nobel Prize recognizes the effort of research that, being largely on basic cellular mechanisms, has had enormous relevance in the treatment of patients with various diseases, whose common basis is the alteration in the supply of oxygen to the cells.