Grant: Project Grant

Canadian life expectancy is increasing but with this improvement the rates of cardiovascular disease, stroke and dementia are rising. This has a major impact on the Canadian and global health burden. Causes of these diseases are due to many factors, however high blood pressure (hypertension) is a common feature. Hypertension is characterized by damage and inflammation of small blood vessels, which may play an important role in the complications of high blood pressure that lead to heart and kidney disease and stroke. Although there are many drugs to treat hypertension, the control of high blood pressure is sub-optimal and the prevalence of uncontrolled hypertension continues to grow worldwide. This may relate to progressive damage of small blood vessels. Therapies to prevent or reverse vessel injury is a medical challenge, since exact causes that regulate vessels remain unclear. Based on studies in our laboratory, we identified an enzyme called Nox5 that may be important. Nox5 produces harmful molecules (reactive oxygen species) that cause damage to cells in the wall of blood vessels. In this study we hypothesize that abnormal activation of Nox5 produces excessive amounts of harmful reactive oxygen species, which lead to vascular damage in patients with high blood pressure. The proposal will examine how Nox5 is regulated in blood vessels, what the mechanisms are that cause an increase activation of Nox5 and how high levels of reactive oxygen species (called oxidative stress) cause injury and inflammation of blood vessels in hypertension. Studies will be performed at the molecular and cellular levels and will also involve models of human disease and patients. The long-term goal of this proposal is to identify new mechanisms and targeted therapies that will promote vessel health and prevent hypertension-associated complications. This will ultimately lead to reduced burden of cardiovascular disease and improved societal health.