High blood pressure or hypertension runs in the blood vessels of 75 million people older than 20 and leads to heart disease, the main cause of death for adults in the United States.
|Matthew Zimmerman, Ph.D.|
"One of the greatest scientific challenges for the improved treatment of brain-related diseases, such as hypertension, is developing therapies that are able to penetrate neurons in the brain," said Matthew Zimmerman, Ph.D., assistant professor in cellular and integrative physiology and director of the Free Radicals in Medicine Program at UNMC.
Through a $1.2 million National Institutes of Health grant, Dr. Zimmerman studies a potentially new therapeutic target in the fight against hypertension and it involves the mitochondria of neurons.
Mitochondria are a source of harmful superoxide radicals, which are produced when neurons are stimulated by angiotensin II (AngII).
In neurons, AngII increases superoxide, which in turn aids AngII-induced neuronal activation. Under normal circumstances, the brain also produces superoxide dismutase (SOD), an antioxidant enzyme that scavenges superoxide and keeps its levels in check.
Trouble comes when AngII levels in the body are chronically elevated as this leads to more superoxide production and a system imbalance. Neurons are continuously activated and mobilize the sympathetic nervous system, which is known to play a key role in hypertension.
Dr. Zimmerman suspects mitochondrial-produced superoxide also plays a key factor in regulating hypertension.
"We are trying to determine if targeting superoxide dismutase in the mitochondria of neurons could be a new therapeutic strategy for treating hypertension," Dr. Zimmerman said.
This work complements Dr. Zimmerman's other, more translational, research, in which he collaborates with the Nebraska Center for Nanomedicine on a nanomedicine-based intervention for hypertension that uses a specially-designed nanozyme to deliver SOD protein to neurons.
Dr. Zimmerman hypothesizes that the SOD nanozyme enters neurons in regions of the brain that lack a blood-brain barrier (BBB). These BBB-deficient brain regions are known to control cardiovascular function.
Increasing protein levels of SOD in these brain regions with the nanozyme will result in lower levels of superoxide and inhibition of AngII-induced neuronal activation.
Recent experiments show that a single injection of the SOD nanozyme inhibits AngII from increasing blood pressure, which could lead to a therapy in the future.