A team of molecular cardiologists at the University of Ottawa has linked a gene, which had never been suspected of playing a role in blood pressure regulation, with human hypertension. The discovery, which was published in the prestigious scientific journal Nature Communications, may lead to new targets that would improve treatments for patients with high blood pressure.
High blood pressure is a major health problem in Canada, where it affects twenty percent of adults. In North America, it is estimated that every year, poorly controlled hypertension leads to some 7 million deaths and 64 million disability-adjusted life years, a measure of health that accounts for the number of years lost due to ill health, disability or early death.
One of the main biological features of hypertension is the narrowing of small blood vessels, which causes blood to exert excessive pressure against the vessel walls and forces the heart to work harder, which can eventually lead to heart failure. However, the underlying events that initiate the cascade leading to hypertension remain poorly understood.
In the new study, the team of scientists led by Dr. Mona Nemer, professor of biochemistry and vice-president, of research at the University of Ottawa, gained new insight by investigating a new mouse model of hypertension and linking their findings to two large studies of human genetics.
The team has identified the GATA5 transcription factor - a member of a protein group that regulates a number of genes in heart cells - as strategically important in regulating blood pressure as well as many of the genes and pathways involved in delivering hormones and nutrients through the blood stream. They observed that an absence of GATA5 in the model was linked to increased blood pressure, dysfunctional blood vessel linings, and age-dependent heart and kidney damage, all of which are symptomatic of high blood pressure in humans.
Our findings in mice who lack GATA5 are consistent with the traits of human essential hypertension and led us to examine the status of this gene in hypertensive individuals. In two independent large cohorts, variants of the GATA5 gene were found in patients suffering from hypertension. Our study opens up new avenues for the prevention of hypertension and its associated health complications, said Professor Nemer.
Lifestyle changes and medication can help control hypertension in some people, but we urgently need new treatments to reduce the staggering death and disability toll due to this condition, said Dr. Duncan Stewart, cardiologist, senior scientist and vice-president of research at The Ottawa Hospital and professor at the University of Ottawa. This research opens the door for the development of a totally new class of hypertension drugs, which could profoundly improve health.
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