Protein responsible for 'bad' blood vessel growth discovered

July 17, 2013

The discovery of a protein that encourages blood vessel growth, and especially 'bad' blood vessels – the kind that characterise diseases as diverse as cancer, age-related macular degeneration and rheumatoid arthritis – has been reported in the journal Nature.

The team at the UCL Institute of Ophthalmology discovered the new protein, called LRG1, by screening for mouse genes that are over-expressed in abnormal in diseased eyes.

In these diseased retinas the LRG1 protein is expressed by blood vessel , which line . LRG1 is also present in the eyes of patients with proliferative diabetic retinopathy – a vascular complication of diabetes that can lead to blindness.

The study shows that, in mouse models, LRG1 promotes the growth of blood vessels in a process known as 'angiogenesis'. Conversely, inhibition of LRG1 in mouse models reduces the harmful blood associated with .

The authors of the study suggest that blocking LRG1's activity is a promising target for future therapy.

Professor John Greenwood, senior author of the research from the UCL Institute of Ophthalmology said: "We have discovered that a secreted protein, LRG1, promotes new blood vessel growth and its inhibition prevents pathological blood vessel growth in ocular disease.

"Our findings suggest that LRG1 has less of a role in normal blood vessel growth and so may be particularly applicable to 'bad' blood vessel growth. This makes LRG1 an especially attractive target for therapeutic intervention in conditions where vessel growth contributes to disease."

Angiogenesis is an essential that is required for development, reproduction and the repair of damaged tissues. However angiogenesis also plays a major role in many diseases where new vessel growth can be harmful.

For example, in the retina uncontrolled and irregular blood vessel growth in diseases such as age-related macular degeneration and diabetic retinopathy can result in a catastrophic loss of vision. Another example is the growth of cancerous solid tumours, which are dependent on the proliferation of new blood vessels. Angiogenesis is also an important feature of , where it contributes to the inflammation of the joint.

In previous studies, many signaling molecules have been identified that control angiogenesis, with the secreted protein vascular endothelial growth factor (VEGF) being considered as the master regulator. Therapeutic targeting of VEGF has resulted in improved outcomes in eye diseases with vascular complications and in some cancers but it is clear that additional therapeutic targets need to be identified.

The mechanism through which LRG1 promotes angiogenesis is by modifying the signalling of a multifunctional secreted growth factor called transforming growth factor beta (TGF-beta). TGF-beta regulates both the maintenance of normal healthy blood vessels, and the unwanted growth of harmful blood vessels, but precisely how it promotes two opposing outcomes is a biological paradox.

This study indicates that in the retinal diseases investigated LRG1 production is 'turned on' in blood vessels. This causes a switch in TGF-beta signalling away from a normal vessel maintenance pathway towards a pathway that promotes the growth of new harmful blood vessels.

Professor Stephen Moss, senior author from the UCL Institute of Ophthalmology said: "Genetic studies have revealed that the gene that codes for LRG1 is conserved in vertebrates, and this study confirms that mouse and human express LRG1.

"We predict, therefore, that abnormal blood vessel growth is also a conserved process and that the role of LRG1 is equally applicable to human pathological angiogenesis."

He added: "Work is already underway to develop a therapeutic antibody that targets LRG1."

Explore further: Cholesterol sets off chaotic blood vessel growth

More information: doi:10.1038/nature12345

Related Stories

Cholesterol sets off chaotic blood vessel growth

May 29, 2013
A study at the University of California, San Diego School of Medicine identified a protein that is responsible for regulating blood vessel growth by mediating the efficient removal of cholesterol from the cells. Unregulated ...

Double drug combo could shut down abnormal blood vessel growth that feeds disease

September 10, 2012
A new study by researchers at Weill Cornell Medical College shows combining two already-FDA approved drugs may offer a new and potent punch against diseases in which blood vessel growth is abnormal—such as cancer, diabetic ...

New molecular pathway regulating angiogenesis may fight retinal disease, cancers

May 29, 2011
Scientists identify in the journal Nature a new molecular pathway used to suppress blood vessel branching in the developing retina – a finding with potential therapeutic value for fighting diseases of the retina and ...

Culprit behind unchecked angiogenesis identified

March 29, 2012
German researchers unravel a critical regulatory mechanism controlling blood vessel growth that might help solve drug resistance problems in the future.

Researchers discover new blood vessel-generating cell with therapeutic potential

October 16, 2012
Researchers at the University of Helsinki believe they have discovered stem cells that play a decisive role in the growth of new blood vessels. If researchers learn to isolate and efficiently produce these stem cells found ...

A coordinated response to cardiac stress

March 1, 2013
Myocardial hypertrophy, a thickening of the heart muscle, is an adaptation that occurs with increased stress on the heart, such as high blood pressure. As the heart muscle expands, it also requires greater blood flow to maintain ...

Recommended for you

Team finds link between backup immune defense, mutation seen in Crohn's disease

July 27, 2017
Genes that regulate a cellular recycling system called autophagy are commonly mutated in Crohn's disease patients, though the link between biological housekeeping and inflammatory bowel disease remained a mystery. Now, researchers ...

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.