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BIDMC investigator to receive vascular biology award from the American Heart Association
Date:3/22/2011

microvasculature walls in coronary artery disease [CAD] may not be just an undesirable by-product," he adds. "Instead, the increased ROS levels found in CAD may be a homeostatic response necessary to increase the synthesis of nitric oxide and thereby increase coronary dilation and blood supply to the heart."

In other words, ROS are also helpful.

Abid's laboratory arrived at this discovery after first studying human endothelial cells from coronary arteries.

"We reduced levels of ROS in these cell cultures, assuming that this would make the cells happy," he explains. "But we came up with totally opposite results. The coronary endothelial cells stopped growing and migrating."

Further investigations revealed that when ROS were reduced, the PI3K-Akt-eNOS pathways which are essential for cell growth and migration and the production of nitric oxide were also experiencing decreased activation. "We thought this might explain why the endothelial cells were so unhappy," says Abid.

To test this hypothesis, the investigators studied an NAPDH oxidase knockout mouse model containing a 50 percent reduction in ROS. (NAPDH oxidase is a major source of ROS in endothelial cells.) After isolating the intact coronary arterioles from the heart of the knockout mouse, as well as those from a wild-type control mouse, Abid's team exposed the coronary blood vessels from both groups of mice to vascular endothelial growth factor (VEGF), a protein known to promote blood vessel growth.

"Normal, healthy blood vessels will become dilated when they are exposed to VEGF," Abid explains. "Conversely, without ROS, the vessels of the knockout mice should have dilated even more when VEGF was introduced." But that wasn't what the scientists found.

"As we had hypothesized, by inhibiting ROS, we were also inhibiting the PI3K-Akt pathway as well as the production of nitric oxide by eNOS. We essentially came to the conclusion that if ROS is
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

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