Nav: Home

Found: the missing ingredient to grow blood vessels

March 13, 2019

Researchers at the University of Virginia School of Medicine have discovered an ingredient vital for proper blood vessel formation that explains why numerous promising treatments have failed. The discovery offers important direction for efforts to better treat a host of serious conditions ranging from diabetes to heart attacks and strokes.

Until now, scientists seeking to grow blood vessels have focused almost exclusively on growing only the inner layer of blood vessels, which are made up of endothelial cells. The hope was that these endothelial cells would then recruit any other cell types needed to form a complete, functional blood vessel. But researchers led by Gary K. Owens, PhD, director of UVA's Robert M. Berne Cardiovascular Research Center, have determined that those vessels can develop properly only if they're grown in conjunction with another cell type, known as perivascular cells, including smooth muscle cells and pericytes. The researchers liken these perivascular cells to the outer support layers of a rubber hose or on automobile tires, without which they burst or leak.

"Most of the studies of angiogenesis [blood vessel formation] have focused on the inner lining of the pipes themselves," researcher Daniel L. Hess said. "That's fairly well understood. But it's really not well understood how you get a complete functional blood vessel that can withstand the mechanical force exerted by blood pressure."

UVA's new discovery helps answer that - and, in so doing, saves scientists from the time, effort and cost of pursuing treatment strategies that will ultimately bear no fruit.

Innovation and Collaboration

The discovery was made possible by the fortuitous convergence of research in two different labs at UVA. Hess was working on a model of peripheral artery disease in the labs of Owens and UVA's Brian Annex, MD, in the Robert M. Berne Cardiovascular Research Center, while another researcher, Molly R. Kelly-Goss, was working with a model of blood vessel growth she developed in the lab of Shayn M. Peirce, PhD, of UVA's Department of Biomedical Engineering.

By bringing those two models together, the researchers were able to determine the vital role of the perivascular cells in blood vessel formation and to identify a gene, Oct4, that is required for this process. Previously, Oct4 had been thought to be active only in embryonic stem cells during early development and to be permanently inactivated in adult organisms. This belief persisted until two years ago, when the Owens lab showed it was reactivated within smooth muscle cells during formation of atherosclerotic plaques inside blood vessels and required for formation of a protective fibrous cap on those lesions that prevents them from rupturing and setting off a heart attack or stroke - analogous to a patch on a tire. Now the lab has shown that Oct4 has an important role in the formation of the vessels themselves - ironically, being required for forming the protective outer wall of blood vessels.

Using Kelly-Goss' model, the researchers were able to examine blood vessel formation in real time. They found that vessels that lacked perivascular cell coverage formed incompletely and leaked blood. "Multiple failed trials assumed the perivascular cells were just passive followers," Owens explained. But without them, he said, "the whole process comes to a halt." Importantly, they found that endothelial cells and perivascular cells communicate with one another via Oct4-dependent processes and, without it, functional non-leaky blood vessels or blood vessel networks cannot form.

Ultimately, that means that scientists must take a more sophisticated approach to growing new vessels, a process important in normal growth and reproduction as well as wound repair.
-end-
Findings Published

The researchers have published their findings in the scientific journal Nature Communications. The research team consisted of Hess, Kelly-Goss, Olga A. Cherepanova, Anh T. Nguyen, Richard A. Baylis, Svyatoslav Tkachenko, Annex, Peirce and Owens.

The work was supported by the American Heart Association, including through Innovative Research Grant 17IRG33370017; the National Institutes of Health, grants R01 HL082838, R01 Ey022063, 1R01 HL12635, 1R01 HL116455, 2R01 HL101200, R01 HL057353, R01 HL135018 and T32 HL007284; the Hartwell Foundation; and the Wagner Fellowship.

To keep up with the latest medical research news from UVA, subscribe to the Making of Medicine blog at http://makingofmedicine.virginia.edu.

University of Virginia Health System

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
More Diabetes News and Diabetes Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.