Wake Forest research confirms controversial nitrite hypothesis

December 12, 2014

WINSTON-SALEM, N.C. - Dec. 12, 2014 - Understanding how nitrite can improve conditions such as hypertension, heart attack and stroke has been the object of worldwide research studies. New research from Wake Forest University has potentially moved the science one step closer to this goal.

In a paper published online ahead of print in the February issue of the Journal of Biological Chemistry, senior co-author Daniel Kim-Shapiro, professor of physics at Wake Forest, and others show that deoxygenated hemoglobin is indeed responsible for triggering the conversion of nitrite to nitric oxide, a process that affects blood flow and clotting.

"We have shown that conversion of nitrite to nitric oxide by deoxygenated hemoglobin in red blood cells reduces platelet activation," Kim-Shapiro said. "This action has implications in treatments to reduce clotting in pathological conditions including sickle cell disease and stroke."

In 2003, Kim-Shapiro collaborated with Mark Gladwin, now at the University of Pittsburgh, who led a study that showed that nitrite (which is also used to cure processed meats), is not biologically inert as had been previously thought, but can be converted to the important signaling molecule nitric oxide (NO), and thereby increase blood flow. At that time, the researchers hypothesized that the conversion of nitrite to NO was due to a reaction with deoxygenated hemoglobin in red blood cells.

The main goal of the latest research, Kim-Shapiro said, was to determine how red blood cells perform these important signaling functions that lead to increased blood flow. The researchers used several biophysical techniques to measure NO production from nitrite and red blood cells and examined the mechanism of NO production.

"Importantly, this action was increased under conditions of low oxygen - so nitrite acts to increase blood flow in the body just when it is needed. What we're showing with this research is what part of the red cell is doing this, and it's consistent with our original hypothesis," he said. "This speaks to the mechanisms and how they work - to how nitrite is dilating blood vessels and reducing clotting."

As director of Wake Forest University's Translational Science Center, Kim-Shapiro and others have conducted studies that look at how nitrite and its biological precursor, nitrate (found in beet root juice) can be utilized in treatments for a variety of conditions. In a 2010 study, they were the first to find a link between consumption of nitrate-rich beet juice and increased blood flow to the brain.

Kim-Shapiro said that next steps in the research include examining whether all red blood cells have this activation function and whether this function is diminished in red cell diseases like sickle cell disease, other blood diseases, or in the transfusion of older blood.

"Does this important function that we can now attribute to the hemoglobin in the red cells get compromised under certain conditions? And if so, how can we enhance it?" he said.
-end-
This work was supported by NIH grants HL058091, HL098032, and the Translational Science Center of Wake Forest University and Hypertension & Vascular Research Center of Wake Forest School of Medicine.

Lead co-authors include Chen Liu and Nadeem Wajih, of WFU department of physics. Contributing authors include Xiaohua Liu, Swati Basu, John Janes, Madison Marvel, Christian Keggi, Amber N. Lee, Andrea M. Belanger, Debra I. Diz, Paul J. Laurienti, and David L. Caudell, all of Wake Forest; Christine C. Helms, University of Richmond; and Jun Wang and Mark T. Gladwin, from the Lung, Blood and Vascular Medicine Institute at the University of Pittsburgh.

Wake Forest University

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.