Research conducted at The Hospital for Sick Children (HSC) has opened up the possibility for a new treatment for pulmonary hypertension that may also be applicable to all types of blood vessel obstruction. This research is reported in the June issue of the scientific journal Nature Medicine.
Pulmonary hypertension results from obstruction of the blood vessels of the lung. It is a common complication of most heart and lung diseases, and it leads to heart failure. Pulmonary hypertension can also occur more rarely as a rapidly progressive and fatal condition that requires chronic intravenous therapy, or a lung or heart-lung transplant.
"We were able to completely reverse fatal pulmonary hypertension in an animal model using an elastase inhibitor. Not only did it stop the progression of the disease, but the blood vessel reverted to a normal condition," said Dr. Kyle Cowan, who carried out the study as a doctoral student under the supervision of Dr. Marlene Rabinovitch, head of the Cardiovascular Research program in HSC’s Research Institute.
Elastase is an enzyme that causes cells in blood vessels to rapidly divide, so that the vessel becomes obstructed. Dr. Rabinovitch’s laboratory used a synthetic, chemical compound (a serine elastase inhibitor) to induce the cells to die and the excess connective tissue to be reabsorbed, thus opening up the blood vessel.
"This research may lead to new avenues in the treatment of many cardiovascular conditions, including the serious problem of pulmonary hypertension. While this study deals with obstructed pulmonary arteries, a similar mechanism may be applicable in reversing coronary disease as well," said Dr. Rabinovitch, holder of the Heart and Stroke Foundation of Ontario Chair at The Hospital for Sick Children, recipient of the Medical Research Council of Canada Distinguished Scientist Award, and a Professor of Paediatrics, Laboratory Medicine and Pathobiology, and Medicine at the University of Toronto.
"Initially, we would like to try the use of an elastase inhibitor with patients who have pulmonary hypertension. The drug which we have tested on animals needs to be developed for clinical trials in humans."
This research was funded by the Heart and Stroke Foundation of Ontario, Medical Research Council of Canada, and the Primary Pulmonary Hypertension Cure Foundation.
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