Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Genetic key to growth of new arteries is identified


Researchers identify key gene sequences that promote growth of new arteries when existing arteries are blocked

Researchers at the San Francisco VA Medical Center have uncovered part of the genetic mechanism that causes new arteries to grow in response to blocked arteries. A team led by SFVAMC vascular surgeon Rajabrata Sarkar, MD, PhD, has demonstrated in mice that the MMP2 gene is essential for the growth of new arteries when the femoral (leg) artery is blocked.

The team also identified and described, for the first time, the specific DNA sequences of the MMP2 gene that are expressed when new arteries are grown. The study appears in the November 8 issue of the Proceedings of the National Academy of Sciences. "It is not clear why some patients grow new arteries in response to an arterial blockage and others do not," observes Sarkar, who is also an assistant professor of surgery at the University of California, San Francisco. "So it’s very important to understand the normal process that allows an animal or a person to grow new arteries when their legs don’t get good blood flow. Legs are a big problem, because if you don’t have enough blood flow, it can eventually lead to gangrene and amputation."

In the first part of the study, Sarkar and his group mimicked human vascular disease in the femoral arteries of normal mice and of mice that lacked the MMP2 gene, which encodes an enzyme that promotes the growth of new arteries. The normal mice grew new arteries, and in about three weeks the blood flow in their legs was close to normal.

The mice without the MMP2 gene did not grow new arteries. About 40 percent lost a portion of a leg due to gangrene caused by inadequate blood flow, demonstrating that the MMP2 gene is "very important" in an animal’s ability to grow new arteries in response to a blockage, says Sarkar.

The second part of the study looked at precisely which areas of the MMP2 gene are activated in skeletal muscles where blood flow is decreased.

The researchers mimicked arterial blockage in transgenic mice created by David Lovett, MD, chief of nephrology at SFVAMC, professor in residence of medicine at UCSF, and one of the co-authors of the study. The mice carried a marker gene, beta galactosidase, that turns tissues blue. Different strains of the mice had different fragments of the MMP2 gene coupled to the so-called blue gene. Leg muscles turned blue only in the strain of mice with the specific gene fragment that turns on in response to arterial blockage.

In this way, the researchers identified and described previously unknown areas of the MMP2 gene, plus other molecules that activate those areas, that are essential to expression of the gene in response to decreased blood flow.

"It’s a very time-consuming approach, but a very elegant way to deal with the problem," comments Sarkar. "This paper is a very fundamental examination of the mechanisms involved in gene regulation in the growth of arteries." The next research step, according to Sarkar, will be to carry out the same experiments in animal models of the various conditions known to cause vascular disease: cigarette smoking, high cholesterol, diabetes, and hypertension.

"For each of these models we will ask, one, is expression of MMP2 impaired, and two, if there is less arterial growth," Sarkar says. "Then if both of those are true – and we think they will be – then we can identify the mechanisms by which expression of MMP2 is blocked."

Over the long term, Sarkar plans to study the same genetic mechanisms in humans, "perhaps in tissue samples taken from patients at the time of surgery." He hopes that eventually, his research will lead to new clinical treatments for arterial blockage in patients.

"As a vascular surgeon, I take care of people who have problems with poor blood flow to different parts of their bodies," he notes. "One thing we know for sure: our patients do not grow new arteries, and that’s why I have to operate on them."

Other co-authors of the study were Jackie G. Lee, BS; Sia Dahi, BS; Rajeev Mahimkar, PhD; Nathaniel L. Tulloch, BS; and Maria A. Alfonso-Jaume, MD, all of SFVAMC.

Steve Tokar | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>