A new mechanism of blood pressure regulation, discovered in animal models, could pave the way for a broader understanding of the causes of hypertension. It is a new perspective on a global health problem, linked to serious pathologies such as heart attacks, strokes and cognitive impairment. The research, published in the scientific journal Circulation Research, was born from a close teamwork of various laboratories of the Irccs Neuromed of Pozzilli (Isernia) in collaboration with Italian universities and research centres. At the center of the study – reads a note – the protein Dickkopf-3 (Dkk3), known to be involved in various functions, from tissue regeneration to angiogenesis (formation of new blood vessels) to the response to oxidative stress.
What the researchers have now discovered is that the Dkk3 protein is also implicated in the regulation of blood pressure. “The study – says Dr. Carla Letizia Busceti, from the Neurobiology of movement disorders laboratory, Department of Molecular Pathology of Neuromed – was first conducted in mice lacking the gene that codes for the Dickkopf-3 protein, in which blood pressure was higher than normal. We saw that, by restoring the presence of Dkk3 in the peripheral or cerebral level, the pressure normalized. We then moved on to other animal models, in particular some rats which tend to be spontaneously hypertensive and vulnerable to onset of stroke. In them, the induction of an increase in the expression of the Dkk3 protein was also shown in this case capable of lowering blood pressure, while at the same time we saw that the onset of stroke was clearly delayed”.
Dkk3 would act by regulating the activity of vascular endothelial growth factor (Vegf), a protein involved in a variety of both physiological and pathological functions, mainly related to the formation of new blood vessels (angiogenesis). Anti-Vegf drugs – continues the note – are currently in use for some pathologies of the retina and for some types of cancer. It should be emphasized that one of the side effects of this treatment is the increase in blood pressure.
“Dickkopf-3 – comments Carmine Vecchione, full professor of Cardiology, University of Salerno, and head of the Neuromed Vascular Physiopathology Research Laboratory – is a protein that is still little known, and we think that our research opens up interesting perspectives in this field . Its involvement in the regulation of blood pressure could in fact offer new insights towards understanding the mechanisms underlying this insidious pathology. Obviously we are in a very early stage, and more studies will be needed to investigate the role of Dkk3 and begin to hypothesize how this knowledge can be applied for prevention and therapeutic perspectives in humans”.
“The study – underlines Speranza Rubattu, full professor of Applied Medical Technical Sciences, Sapienza University of Rome and head of the Experimental Bases of Cardiovascular Pathology Unit at Neuromed – also offers a clear demonstration of the relevance of the experimental research, conducted in appropriate models animals, for the deepening of our knowledge in medicine.In fact, both the hypertensive mouse and rat models have been of fundamental importance for the discovery and characterization of the function of Dkk-3 in the regulation of blood pressure. previous evidence of the translationality of data obtained in the hypertensive rat model to human disease, we expect that the role of Dkk-3 will also be confirmed in humans”.
“This research – underlines Ferdinando Nicoletti, full professor of Pharmacology, Sapienza University of Rome and head of the Neuromed Neuropharmacology Laboratory – shows us how our neuroscience-oriented Irccs also hosts some of the best research groups specialized in the study of cardiovascular diseases These are fields of research that intersect and pave the way for new therapeutic strategies”. The Neuropharmacology Laboratory, the Neurobiology and Movement Disorders Unit, the Vascular Pathophysiology Laboratory and the Experimental Bases of Cardiovascular Pathology Laboratory of the Pozzilli Institute participated in the study.
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