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

BOSTON -- Alterations in blood vessel dilation lie at the heart of coronary artery health: When vessels dilate, blood and oxygen supplies successfully reach the heart. When vessels contract, blood and oxygen are diminished, leading to coronary artery disease.

The biology behind this course of events, known as vasodilation, occurs through nitric oxide, a gaseous molecule synthesized by an enzyme called eNOS, which relaxes the vascular smooth muscle cells lining the outer layer of coronary vessels. If, during this course of events, nitric oxide (NO) encounters another group of molecules known as reactive oxygen species (ROS), then NO is inactivated, and instead of dilating, blood vessels contract. In other words, ROS are harmful.

But a paper by Ruhul Abid, MD, PhD, of BIDMC's Center for Vascular Biology Research upends this long-held notion, demonstrating that ROS has another, beneficial role in the activation of eNOS and the nitric oxide production process and, in fact, is necessary to maintain coronary vasodilation.

This paradoxical discovery, published last spring in the American Heart Association journal Arteriosclerosis, Thrombosis, and Vascular Biology, was recently selected from more than 650 entries as the journal's most outstanding Vascular Biology paper of 2010. Abid will receive the AHA's 2011 Werner Risau New Investigator Award in Vascular Biology on April 29 in Chicago for this groundbreaking work.

"ROS are generally believed to play harmful roles in microvascular tone in hypertension, angiogenesis and vascular complications of arthritis and diabetes," explains Abid. "As a result, it's been widely assumed that by reducing ROS oxidants, you can improve cardiovascular function." In fact this is the premise underscoring the use of antioxidants, such as Vitamins E and C and beta carotene, to help prevent heart disease.

"But our findings now suggest that these high oxidant levels often found in the 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 reduced too much, blood vessels contract instead of dilate, and adequate blood supply is unable to reach the heart."

"Dr. Abid has made an important discovery regarding the role of oxidative stress on VEGF signaling in the vasculature," notes Frank Sellke, MD, PhD, the Karl Karlson and Gloria Karlson Professor and Chief of Cardiothoracic Surgery at Brown Medical School and Lifespan Hospitals. "This may have relevance in clinical medicine, especially as it applies to atherosclerotic heart disease and regenerative medicine."

According to Abid, follow-up studies will help guide investigators and clinicians as to whether or not to interfere with the high redox levels often present in coronary microvascular disease.

"As we have now learned, by lowering oxidant levels you could be paradoxically affecting redox-dependent signaling and vasodilation, and therefore, predisposing patients to an increased risk of myocardial ischemia. Going forward, we aim to understand the permissive role of ROS in maintaining coronary vasodilation," he adds. "We think this may have an impact on the development of therapeutic modalities for vascular diseases, and may help explain the apparent failure of antioxidants in large clinical trials, such as the HOPE trial."

The AHA's Werner Risau New Investigator Award in Vascular Biology was established in honor of Dr. Werner Risau, an investigator who formulated key concepts for the regulation of angiogenesis, challenged the prevailing dogmas about angiogenic factors, and proposed the now accepted hypothesis that several growth factors act sequentially to mediate vasculogenesis, angiogenesis, and vascular remodeling.


'/>"/>

Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
Source:Eurekalert

Related medicine news :

1. BIDMC researcher receives Young Investigator Award from Prostate Cancer Foundation
2. Scott & White Healthcare pathologist is co-investigator on breast cancer study
3. SEBM Young Investigator Awards for 2010
4. BUSM researcher receives prestigious young investigator award
5. Investigators examine colorectal cancer screening methods among diverse populations
6. University of Utah afib specialist, Marcos Daccarett, M.D., wins Young Investigator Award
7. UT Southwestern investigators perform head-to-head comparison of incontinence treatments
8. Damon Runyon Cancer Research Foundation awards $3.1M to 8 top young clinical investigators
9. Investigators identify gene associated with kidney disease in African-American population
10. SWOG names 5 cancer researchers outstanding Young Investigators
11. NCH investigators receive grant to distinguish bacterial infections from viral infections in infants
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/5/2016)... ... 2016 , ... Dr. Justin Scott and Dr. Lydia Muccioli of Pure ... to individuals in need. The event is scheduled to take place on February 27, ... to provide dental care to community members in need. Each patient will be given ...
(Date:2/5/2016)... ... February 05, 2016 , ... Dr. Ben Amini, ... it is now welcoming orthodontist, Dr. Amanda Cheng, to the practice. With the ... oral health care, including general dentistry, cosmetic treatments, periodontics, implant dentistry , ...
(Date:2/5/2016)... Pekin, IL (PRWEB) , ... February 05, 2016 , ... ... in disguised form as a dream. A hallmark feature of patients with eating disorders ... and needs. The eating disorder behaviors and obsessions are regarded as maladaptive means for ...
(Date:2/5/2016)... ... February 05, 2016 , ... California Mobile ... the debut of their latest mobile kitchen model, featuring customizable stainless steel interiors ... high-volume commercial kitchens for use anywhere in the U.S. Many of their units ...
(Date:2/5/2016)... Russia (PRWEB) , ... February 05, 2016 , ... Calls ... has a completely new user interface design and the developer has fixed known bugs ... those they want to on their phone while not consuming any of their device’s ...
Breaking Medicine News(10 mins):
(Date:2/4/2016)... Global Immunology Market to 2022 - ... market growth Summary Immune-mediated inflammatory diseases ... that affect 5–7% of western populations. Although they ... and key patient demographics, they are pathophysiologically linked, ... an inappropriate immune response. Generally, disease-modifying anti-rheumatic drugs, ...
(Date:2/4/2016)... Feb. 4, 2016 Mettler-Toledo International Inc. (NYSE: ... 2015.  Provided below are the highlights: , ... compared with the prior year.  Reported sales decreased 3% ... quarter. , Net earnings per diluted share as ... prior- year period.  Adjusted EPS was $4.65, an increase ...
(Date:2/4/2016)... 4, 2016  AMRI (NASDAQ:  AMRI) today announced that ... and President of Pfizer Global Supply, has been elected to ... 2016. In addition, the Company announced that Mr. Gabe ... since 2010, has retired from the AMRI Board of Directors ... other business ventures.  William S. Marth , ...
Breaking Medicine Technology: