Work on a doctoral dissertation at Umeå University in Sweden led to the discovery of new blood biomarkers reflecting vasoreactivity in lung blood vessels of patients with heart and lung disease, which can lead to simplified diagnostics and better treatment evaluation in patients with pulmonary arterial hypertension (PAH). L-arginine and dimethylarginines, the novel blood biomarkers, are known to be involved in the inhibition of nitric oxide production, a vasodilator.
“We have discovered that the biomarkers that we have investigated have a particularly high diagnostic value in PAH, by comparing with heart failure and healthy individuals. These biomarkers have the potential to be used as a routine diagnostic strategy and in the evaluation of PAH patients,” said Anna Sandqvist, a doctoral student at the Department of Pharmacology and Clinical Neuroscience and the dissertation’s author, in a news release.
“Since the levels of these markers in the blood are reflecting the clinical efficacy of PAH-specific medical treatment, there is good hope that they soon can be used routinely to measure treatment response. The results are so far based on around 20 PAH patients, which means that more research is necessary on larger patient groups,” Sandqvist added.
PAH is a multi-organ condition characterized by an abnormally high pressure in the network of arteries and veins that lead to and from the lungs due, in part, to narrowing of the pulmonary vasculature as a result of inflammation, remodeling, proliferation, and endothelial dysfunction. PAH patients experience increased pressure on the right side of the heart, which can lead to ventricular failure and death.
The prognosis of PAH is poor, and there are only a few appropriate methods for disease diagnosis and treatment. Patients with PAH are usually treated with drugs that reduce pulmonary artery pressure by dilating the blood vessels.
In her doctoral work, Sandqvist also suggests a new drug to treat PAH called vardenafil. Vardenafil belongs to a class of medications called phosphodiesterase (PDE) inhibitors that have vasodilator properties, and are usually used to treat erectile dysfunction in men.
“Vardenafil has a fast onset and powerful effect on the blood vessels of the lungs. But if vardenafil is used in combination with the endothelin receptor antagonist bosentan — another pharmaceutical often used by patients with PAH — the effect of treatment can be hampered and lead to the need of increasing the dosage of vardenafil. Therapeutic drug monitoring may thus become necessary to check the pharmaceutical concentrations in the blood in order to optimise the dosage,” she said.