Nav: Home

Feeling the pressure: How blood vessels sense their environment

April 24, 2020

Tsukuba, Japan - Cells and tissues are far from being mere static structures. They have the ability to sense and dynamically react to external cues to ensure that they adapt to the ever-changing outside environment. Now, researchers from the University of Tsukuba have identified a novel protein that plays a central role in the transduction of external mechanical cues to cells in blood vessel walls. In a new study, they show how the protein thrombospondin-1 (Thbs1) ensures that blood vessel walls are strengthened during times of mechanical stress and conversely, how the absence of Thbs1 can result in weakened blood vessel walls.

All tissues, including blood vessels, are composed of different types of cells and proteins surrounding them, the latter also being called extracellular matrix (ECM). The ECM not only ensures that cells are stably anchored to an outside structure, but also serves as a means to transmit mechanical impulses. In blood vessels, the most important mechanical cues stem from the pulsatile blood flow as well as the constantly changing blood pressure. While a large number of proteins have been described to play a role in the interplay between cells and the ECM, a clear understanding of how this mechanical microenvironment is coordinated to maintain the structural and functional integrity of blood vessels has been lacking.

"Blood vessels are constantly exposed to strong mechanical forces from the outside, so they have to adapt to them by translating these cues into proper cellular responses," says corresponding author Professor Hiromi Yanagisawa. "The goal of our study was to further our understanding of the interaction between blood vessels and mechanical stress during normal biology and during times of high stress, such as in hypertension."

To achieve their goal, the researchers exposed rat vascular smooth muscle cells (SMCs) to cyclic stretch to mimic pulsatile blood flow and found that mechanical stress resulted in SMCs producing more Thbs1 and secreting it. They then discovered that Thbs1 interacted with certain integrins, a protein family that links cells to the ECM, to strengthen so called focal adhesions, which are anchor points that help maintain cellular tension as well as correctly orient cells in response to mechanical stretch.

"These findings show how Thbs1 plays a significant role in the cellular response to relatively mild mechanical stress," says lead author Professor Yoshito Yamashiro. "We next wanted to know how Thbs1 is involved in more extreme cases of mechanical stress, such as during severe hypertension."

To simulate hypertension, the researchers performed transverse aortic constriction (TAC) in mice. TAC forces the heart to pump blood against a severely narrowed aorta, resulting in high blood pressure and high mechanical stress on the aortic wall. Although all normal mice survived this procedure, one third of mice lacking Thbs1 died of aortic rupture as a result of weakened aortic wall due to disrupted interaction between blood vessel wall cells and the ECM.

"These are striking results that show how Thbs1 is a central extracellular mediator of mechanotransduction," says Professor Yanagisawa. "Our findings provide new insights into the biomechanics of the vessel wall, which is relevant to hypertension, one of the most prevalent diseases today. We hope that our findings will facilitate the development of novel therapeutic options for cardiovascular diseases."
-end-
The article, "Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP signaling pathway in the remodeling of blood vessels," was published in Proc. Natl. Acad. Sci. USA

University of Tsukuba

Related Blood Vessels Articles:

Feeling the pressure: How blood vessels sense their environment
Researchers from the University of Tsukuba discovered that Thbs1 is a key extracellular mediator of mechanotransduction upon mechanical stress.
Human textiles to repair blood vessels
As the leading cause of mortality worldwide, cardiovascular diseases claim over 17 million lives each year, according to World Health Organization estimates.
How high levels of blood fat cause inflammation and damage kidneys and blood vessels
Viral and bacterial infections are not the only causes of inflammation of body tissue.
3D printing, bioinks create implantable blood vessels
A biomimetic blood vessel was fabricated using a modified 3D cell printing technique and bioinks.
When blood vessels are overly permeable
In Germany alone there are around 400,000 patients who suffer from chronic inflammatory bowel diseases.
Nicotine-free e-cigarettes can damage blood vessels
A Penn study reveals single instance of vaping immediately leads to reduced vascular function.
Creating blood vessels on demand
Researchers discover new cell population that can help in regenerative processes.
Self-sustaining, bioengineered blood vessels could replace damaged vessels in patients
A research team has bioengineered blood vessels that safely and effectively integrated into the native circulatory systems of 60 patients with end-stage kidney failure over a four-year phase 2 clinical trial.
Found: the missing ingredient to grow blood vessels
Researchers have discovered an ingredient vital for proper blood vessel formation that explains why numerous promising treatments have failed.
How sickled red blood cells stick to blood vessels
An MIT study describes how sickled red blood cells get stuck in tiny blood vessels of patients with sickle-cell disease.
More Blood Vessels News and Blood Vessels 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

Our Relationship With Water
We need water to live. But with rising seas and so many lacking clean water – water is in crisis and so are we. This hour, TED speakers explore ideas around restoring our relationship with water. Guests on the show include legal scholar Kelsey Leonard, artist LaToya Ruby Frazier, and community organizer Colette Pichon Battle.
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

Uncounted
First things first: our very own Latif Nasser has an exciting new show on Netflix. He talks to Jad about the hidden forces of the world that connect us all. Then, with an eye on the upcoming election, we take a look back: at two pieces from More Perfect Season 3 about Constitutional amendments that determine who gets to vote. Former Radiolab producer Julia Longoria takes us to Washington, D.C. The capital is at the heart of our democracy, but it's not a state, and it wasn't until the 23rd Amendment that its people got the right to vote for president. But that still left DC without full representation in Congress; D.C. sends a "non-voting delegate" to the House. Julia profiles that delegate, Congresswoman Eleanor Holmes Norton, and her unique approach to fighting for power in a virtually powerless role. Second, Radiolab producer Sarah Qari looks at a current fight to lower the US voting age to 16 that harkens back to the fight for the 26th Amendment in the 1960s. Eighteen-year-olds at the time argued that if they were old enough to be drafted to fight in the War, they were old enough to have a voice in our democracy. But what about today, when even younger Americans are finding themselves at the center of national political debates? Does it mean we should lower the voting age even further? This episode was reported and produced by Julia Longoria and Sarah Qari. Check out Latif Nasser's new Netflix show Connected here. Support Radiolab today at Radiolab.org/donate.