Cardiovascular disease

DEFUSING THE TIME BOMB

One out of every four adults is a walking time bomb.

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.

Although there are several drugs to treat hypertension, 20 percent of people with this disease are resistant to current therapy.

"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.

Matthew Zimmerman, Ph.D photo

Radical source

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.

System imbalance

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.

Complementary work

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.

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