Can blocking RhoB activation prevent lung damage in pulmonary hypertension?

RhoB inhibitors in prevention and treatment of chronic hypoxia-induced pulmonary hypertension.

Pulmonary hypertension is a serious condition in which high blood pressure in the arteries of the lungs results in narrowing of these blood vessels. Patients can have a poor quality of life and are at risk of developing heart failure because the heart has to work hard to pump against the high blood pressure in the lungs. Dr Beata Wojciak Stothard and colleagues from Imperial College London are investigating novel ways to treat pulmonary hypertension. Pulmonary hypertension can arise as a result of a low oxygen state in the body. To ensure that enough oxygen gets to the heart, the body’s circulatory system adapts by constricting the blood vessels in the lungs. However, this carries the consequence of damage to the lung vessels. Researchers have previously identified that when oxygen is low, a protein called RhoB is activated. This team proposes that activated RhoB plays a part in the development of pulmonary hypertension. They will investigate in mice whether blocking the activation of RhoB with a drug called tipifarnib may prevent damage to blood vessels in the lung. Tipifarnib is currently being tested in clinical trials for the treatment of cancer. In a further novel approach, they will also look at whether blocking the particular gene that leads to RhoB production in mice also improves the health of the lung circulation. Their findings will pave the way for further important future research on preventing the damaging action of RhoB in conditions of low oxygen.