Navigation Links
Mayo Clinic-led study unravels biological pathway that controls the leakiness of blood vessels
Date:12/17/2012

JACKSONVILLE, Fla. A research team led by scientists at Mayo Clinic in Florida have decoded the entire pathway that regulates leakiness of blood vessels a condition that promotes a wide number of disorders, such as heart disease, cancer growth and spread, inflammation and respiratory distress.

They say their findings, published online Dec. 17 in the Journal of Cell Biology, suggest that several agents already being tested for other conditions might reverse vessel leakiness.

"Now that we understand a lot more about the pathway that leads to leaky blood vessels, we can begin to try to target it in an efficient way, and that is very exciting," says the study's lead investigator, Panos Z. Anastasiadis, Ph.D., chair of the Department of Cancer Biology at Mayo Clinic in Florida.

Physicians have attempted to regulate that pathway in cancer through use of VEGF inhibitors, such as Bevacizumab, but these drugs are not as effective as they might be if other parts of the pathway were also inhibited, Dr. Anastasiadis says.

The research team, led by Dr. Anastasiadis and Arie Horowitz, Ph.D., at Cleveland Clinic Foundation, found that VEGF is one of two different molecules that affect a key downstream protein, Syx, to regulate the permeability of blood vessels.

Blood vessels are made up of endothelial cells that have to fit tightly together to form a solid tubular structure that blood can flow through. The researchers discovered that VEGF turns off Syx, which normally ensures the junctions between endothelial cells are strong. Without Syx, adhesion between the cells is loose, and the blood vessels are leaky. When new blood vessels are needed such as to feed a growing tumor VEGF loosens up endothelial cells so new vessels can sprout.

Then, after new vessels are formed, a second molecule, angiopoietin-1 (Ang1) works to glue the cells back together, Dr. Anastasiadis says. "These molecules have opposing, yin and yang effects. VEGF kicks Syx out of the junctions between cells, promoting leakiness, and Ang1 brings it back in to stabilize the vessel," he says.

The issue in cancer, however, is that VEGF overwhelms the system. "There isn't enough Ang1 to glue the vessels back together, and this leakiness allows cancer cells to escape the tumor and travel to other parts of the body," Dr. Anastasiadis says. "In late stages of the cancer, it also promotes the leaking of liquids into organs, such as the lungs. This results in profound effects that are often lethal."

Other disorders, such as inflammation and sepsis, a deadly bacterial infection that can result from excess liquid in lungs, are also induced by a leaky vascular system, he says.

Based on a detailed analysis of molecules involved in the VEGF/Ang1/Syx pathway, Dr. Anastasiadis believes that several experimental agents might help reverse vascular leakiness. One of them inhibits protein kinase D1 (PKD1), which might prevent endothelial cells from coming apart from loss of adhesion, and the other is a Rho-kinase inhibitor that prevents endothelial cells from contracting which they must do to loosen up and become leaky.

"We now have new directions for both further basic research into leaky blood vessels and for potential clinical treatment," Dr. Anastasiadis says.

Investigators from Johns Hopkins University, Dartmouth Medical School, and Case Western Reserve University also contributed to the study.


'/>"/>

Contact: Kevin Punsky
punsky.kevin@mayo.edu
904-953-2299
Mayo Clinic
Source:Eurekalert

Related medicine news :

1. Study shows COPD is not independent risk factor for lung cancer
2. Study questions reasons for routine pelvic exams
3. Study Questions Advice Given to Obese Pregnant Women
4. Back Pain May Ease for Smokers Who Quit: Study
5. Immune System May Not Weaken With Age: Study
6. High Blood Pressure Poses Bigger Stroke Risk for Blacks, Study Says
7. Cedars-Sinai physician-scientist awarded $3M to study most common inherited neurological disorder
8. Study shows antidepressant could do double duty as diabetes drug
9. Yo-Yo Dieting Can Hurt the Heart, Study Finds
10. Legal Unions, Including Marriage, Boost Mental Health for Gay People: Study
11. Workplace Bullying Takes Toll on Witnesses Too, Study Finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:12/2/2016)... ... , ... Mediaplanet is proud to announce the launch of ... treatments, therapeutic technologies, and revolutionized nutrition that are helping patients and physicians manage ... in the last 3 decades,” says Dr. Valentine Fuster, a world-renowned cardiologist. “This ...
(Date:12/2/2016)... ... , ... Rijuven Corp launches rejiva ( http://www.rejiva.com ), a unique wearable technology ... health technology on the market can deliver all that rejiva can. , “Rejiva promotes ... their health than the usual heart rate and steps taken”, adds Evens Augustin, CEO ...
(Date:12/2/2016)... ... December 02, 2016 , ... Today ... intelligent, connected applications, was named the best Sales Team of 2016 as part ... was made today by the Software & Information Industry Association (SIIA), the principal ...
(Date:11/30/2016)... ... , ... "I hate when the mixture of saliva and toothpaste runs down ... from Bridgewater, N.J. "I thought that there had to be a way to prevent ... patent-pending DEFLECTOR to prevent saliva and toothpaste from running down the brush handle onto ...
(Date:11/30/2016)... U.K. (PRWEB) , ... November 30, 2016 , ... ... address the tech functions and stylish design wanted by today’s consumers at an ... Cronovo Co-Founder Darin Philip says the new watch is “a game changer” when ...
Breaking Medicine News(10 mins):
(Date:12/2/2016)... WOONSOCKET, R.I. , Dec. 2, 2016 ... hold its annual Analyst Day in New York City on Thursday, December ... the CVS Health leadership team will provide an in-depth ... and enhance shareholder value. The company will also discuss ... audio and video webcast of the event will be ...
(Date:12/2/2016)... 2, 2016 Orthopedic Implants (Including Spinal ... Expected to Gain a Significant Market Share Owing to a ... ... According to a new report by ... Sterile Packaging: Clamshell Product Type Segment Projected to Witness a ...
(Date:12/2/2016)... N.J. , Dec. 2, 2016   CytoSorbents ... immunotherapy leader commercializing its European Union approved CytoSorb ... and cardiac surgery patients worldwide, announced that Dr. ... the 9th Annual LD Micro Main Event ... , 2016 at the Luxe Sunset Boulevard Hotel in ...
Breaking Medicine Technology: