Hypertension

High blood pressure increases the risk of heart attack, stroke and heart failure. This makes hypertension one of the most important causes of death or permanent injury in the world. However, in 95 percent of all cases, the molecular mechanisms that causes hypertension are unknown. As a result, patients are often treated with drugs that widen the blood vessels and merely treat the symptoms of high blood pressure while leaving the cause untreated. Most patients therefore continue to contend with the long-term consequences of hypertension, such as heart attacks or stroke. In contrast, the cause of high blood pressure that these scientists have now found can be treated with existing and already registered drugs. “With the support of the European Society of Hypertension, we have compiled a world-class team of clinical scientists and just wait for the final funding approval to conduct the international, multi-centre HYPERNET study to test the efficacy of our treatment”, says Prof. Harald Schmidt from Maastricht University.

Oxygen radicals

Scientists have long suspected that hypertension is the result of oxygen radicals in the blood vessel walls, which disrupt a protective but very sensitive so-called cGMP signalling pathway. Normally, this signalling pathway helps prevent arterial narrowing and thrombosis. The research team used big data to identify the Nox5 protein as the main source of these oxygen radicals. In a group of patients with high blood pressure, the researchers detected higher levels of Nox5. This protein is specific to humans and not found in laboratory animals such as mice or rats. However, when the scientists genetically engineered mice to have the human Nox5 protein, the animals also developed severe hypertension and decreased blood vessel function with age. This happened because the protein also disrupted cGMP signalling in mice. Thus, interaction of the Nox5 and the cGMP signalling pathway is the first causal mechanism of primary hypertension identified in humans. “It is fascinating to see how systems medicine can unravel the origin of diseases that we previously could only characterize based on symptoms, such as primary hypertension”, says Prof. Martin Paul, President of Maastricht University and a well-known expert on hypertension. “I am also pleased that this publication is an excellent example of team science, bringing together renowned scientists under the leadership of Professor Schmidt and his Maastricht group.”