Nav: Home

New findings on formation and malformation of blood vessels

May 22, 2017

In diseases like cancer, diabetes, rheumatism and stroke, a disorder develops in the blood vessels that exacerbates the condition and obstructs treatment. Researchers at Karolinska Institutet now show how blood vessels can normally change their size to create a functional circulatory system and how vascular malformation during disease can occur. In the study, published in Nature Cell Biology, the researchers managed to treat vascular malformation in mice, a discovery of potential significance to numerous vascular diseases.

A healthy body has a perfect balance of arteries, capillaries and veins that allow the blood to reach every cell in the body and that form what is called the "vascular tree". New blood vessels are formed by endothelial cells, which normally coat the inside of blood vessels and which organise themselves into tubes and mature, along with other cells, into arteries, capillaries or veins.

Throughout a person's life, the vascular tree has to adapt its branches to the changing needs of body tissue, such as during growth, muscle building or wound healing. However, there are diseases that affect the endothelial cells in a way that throws the vascular tree out of balance, which exacerbates the disease and often causes haemorrhaging. In cancer, for example, it is known that the vessels leak and direct shunts form between arteries and veins, preventing drugs from reaching the tumour.

To understand how arteries, veins and capillaries are created - and how the process malfunctions in the presence of disease - the researchers studied normal vascular formation and the inherited Osler-Weber-Rendu disease (HHT), which is characterised by vascular malformation and repeated haemorrhaging, with an increased risk of stroke. By switching signals on and off in the endothelial cells of genetically manipulated mice, the researchers could describe how the protein Endoglin controls vascular formation and malformation. They found that the protein acts like a sensor that detects blood flow and tells the endothelial cells to organise themselves into veins, capillaries or arteries as necessary. Cells that lacked the protein were less able to form arteries.

The researchers were also able to reduce vascular malformation in the genetically manipulated mice.

"Our findings contribute to the understanding of fundamental biological processes that explain how the vascular tree is formed and what causes vascular malformation," says Lars Jakobsson, assistant professor at Karolinska Institutet's Department of Medical Biochemistry and Biophysics. "Drugs with a similar effect as one of those we tested are currently used to treat patients with inherited vascular malformation but are still under evaluation. Now we have another candidate and a more nuanced idea of how it works. We are now in a better position to control the formation and malformation of blood vessels and thus their function, which can eventually lead to improved treatments for a number of diseases."

The researchers at Karolinska Institutet also contributed to a parallel study, published in the same issue of Nature Cell Biology, describing how blood flow influences endothelial cell size that in turn affects vessel identity and malformation.
-end-
The studies were financed by several bodies, including the William K. Bowes, Jr. Foundation, the Swedish Research Council, the Swedish Cancer Society, Karolinska Institutet, the Jeansson Foundations and the Magnus Bergvall Foundation.

Publications: "Endoglin prevents vascular malformation by regulating flow-induced cell migration and specification through VEGFR2 signalling". Yi Jin, LarsMuhl, Mikhail Burmakin, YixinWang, Anne-Claire Duchez, Christer Betsholtz, Helen M. Arthur and Lars Jakobsson. Nature Cell Biology, online 22 May 2017, doi: 10.1038/ncgb3534

"Endoglin controls blood vessel diameter through endothelial cell shape changes in response to haemodynamic cues". Wade W. Sugden, RobertMeissner, Tinri Aegerter-Wilmsen, Roman Tsaryk, Elvin V. Leonard, Jeroen Bussmann, Mailin J. Hamm, Wiebke Herzog, Yi Jin, Lars Jakobsson, Cornelia Denz, Arndt F. Siekmann. Nature Cell Biology, online 22 May 2017, doi: 10.1038/ncb3528

Karolinska Institutet

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Processing The Pandemic
Between the pandemic and America's reckoning with racism and police brutality, many of us are anxious, angry, and depressed. This hour, TED Fellow and writer Laurel Braitman helps us process it all.
Now Playing: Science for the People

#568 Poker Face Psychology
Anyone who's seen pop culture depictions of poker might think statistics and math is the only way to get ahead. But no, there's psychology too. Author Maria Konnikova took her Ph.D. in psychology to the poker table, and turned out to be good. So good, she went pro in poker, and learned all about her own biases on the way. We're talking about her new book "The Biggest Bluff: How I Learned to Pay Attention, Master Myself, and Win".
Now Playing: Radiolab

Invisible Allies
As scientists have been scrambling to find new and better ways to treat covid-19, they've come across some unexpected allies. Invisible and primordial, these protectors have been with us all along. And they just might help us to better weather this viral storm. To kick things off, we travel through time from a homeless shelter to a military hospital, pondering the pandemic-fighting power of the sun. And then, we dive deep into the periodic table to look at how a simple element might actually be a microbe's biggest foe. This episode was reported by Simon Adler and Molly Webster, and produced by Annie McEwen and Pat Walters. Support Radiolab today at Radiolab.org/donate.