Boffins identify ‘gas pedal’, ‘brake’ for uncontrolled cell growthAugust 2nd, 2010 - 5:10 pm ICT by ANI
London, Aug 2 (ANI): Scientists have found a new way to regulate the uncontrolled growth of blood vessels, a major problem in a broad range of diseases and conditions.
The findings of the study, conducted by researchers at the University of California, San Diego School of Medicine, have appeared in the online edition of Nature Medicine.
Blood vessels grow and expand in association with a number of diseases. In particular, new blood vessel growth (known as angiogenesis) occurs during the growth of tumors, enabling them to expand and metastasize or spread to other parts of the body.
Uncontrolled vascular growth can lead to vascular malformations and hemangiomas, which may become life-threatening. According to the National Cancer Institute, as many as 500 million people worldwide could benefit from therapies targeting angiogenesis.
Researchers have been trying to identify the switch mechanism that converts normal blood vessels from the resting state to the proliferative or diseased state. Cheresh, along with the study’s first author Sudarshan Anand, also of the UCSD School of Medicine and the Moores Cancer Center, and colleagues discovered how an “angiogenic switch” turns on and developed a strategy to turn it back off.
During normal blood vessel formation or regeneration, endothelial cells forming the inner layer of blood vessels are exposed to factors in the local microenvironment that initiate the switch, causing blood vessels to begin to expand. Cheresh and colleagues identified a small microRNA (miR-132) responsible for controlling the switch.
David A. Cheresh, professor of pathology in the UC San Diego School of Medicine, described the process in terms of a car and its brakes: “In tumour vessels or in hemangiomas, this particular microRNA is abundant and capable of maintaining extensive vascular growth. The effect is similar to a car that’s speeding out of control because its gas pedal is stuck to the floor and its brakes aren’t working.”
The researchers designed a complementary microRNA, or anti-miR, that binds to and neutralizes the original microRNA.
“This anti-miR therapy in effect restores functionality to the brake pedal and uncontrolled blood vessel growth comes to a halt,” said Cheresh, who noted the new anti-miR turned off the angiogenic switch controlling disease severity in mouse models of cancer and of retinal disorders.
As part of their study, Cheresh and colleagues designed a nanoparticle that’s capable of delivering the microRNA or the anti-microRNA directly to the diseased or proliferating blood vessels. This delivery vehicle ensures the therapeutic benefit is maximized while reducing the possibility of toxicity or side effects.
By delivering more of this microRNA, the scientists said, it may be possible to promote new blood vessel development in patients who have suffered tissue damage from stroke, heart attacks, or diabetes. Conversely, treating patients with the anti-miR might reduce or inhibit blood vessel development in tumours or help reduce inflammation. (ANI)
- MicroRNAs could increase amputation risk in diabetics - Jan 13, 2011
- New discovery could shrink dengue-spreading mosquito population - Dec 03, 2010
- Indian-origin scientist finds genetic switch that may help treat vascular diseases - Jul 06, 2009
- Bone drug may help prevent spread of early lung cancer - Feb 26, 2011
- Scientists unveil microRNA that controls blood vessel development - Aug 12, 2008
- Morphine may block tumour growth - Jul 29, 2010
- Key step in body's ability to make red blood cells found - Aug 01, 2010
- Lung cancer culprit could offer therapeutic target - Sep 14, 2010
- Micro-RNA that regulates insulin in obesity identified - Apr 01, 2011
- Scientists uncover clues to cancer development in AIDS patients - Jun 18, 2009
- RNA-based drugs may prevent premature labour - Nov 16, 2010
- Autism effects may be reversible - Apr 24, 2010
- Scientists discover cancer treatment in 'junk DNA' - Sep 29, 2010
- Scientists convert skin cells to stem cells more effieciently - Feb 03, 2011
- Body's own molecular protection against arthritis discovered - May 19, 2010
Tags: angiogenic, blood vessel formation, blood vessel growth, california san diego, diseased state, diseases and conditions, endothelial cells, hemangiomas, microenvironment, microrna, national cancer institute, nature medicine, switch mechanism, uc san diego, ucsd school, uncontrolled cell growth, uncontrolled growth, university of california san diego, vascular growth, vascular malformations