Nav: Home

Changes in blood flow tell heart cells to regenerate

June 25, 2019

Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish, says a new study in eLife.

The findings reveal signalling pathways important for heart regeneration in zebrafish that are also present in mammals, providing insights that could help scientists find new ways to repair the organ after a heart attack in future.

Heart muscle cells called cardiomyocytes hold on to the capacity to reprogram themselves and alter their fate in response to heart damage. Although several signalling cues are known to be involved in this regeneration activity, it is not well understood how heart injury switches on these pathways to initiate heart cell reprogramming.

"Recent studies suggest that biomechanical forces generated by blood flow can contribute to heart development through modulating cell signalling," explains lead author Manuel Gálvez-Santisteban, a postdoctoral scientist at the University of California, San Diego (UC San Diego), US. "We wanted to explore this further by seeing whether mechanical forces caused by altered blood flow during heart injury also activate these signalling pathways to control heart cell reprogramming and regeneration."

The team first looked at how heart injury affects signalling of an important heart development molecule called Notch in zebrafish. They found that injury-induced Notch activity peaks at 24 hours after injury but diminishes as the heart regenerates, so that by 96 hours it has returned to normal. If Notch is blocked, however, this prevents heart cell growth and stops heart precursor cells from reprogramming and maturing into cells that can replace the damaged cells.

They next explored whether heart injury could alter blood flow forces and, in turn, control injury-induced Notch signalling. Klf2a is a molecule that responds to changes in blood flow and switches on certain genes in response. In regions of the injured heart where blood flow was most disrupted, they found that levels of Klf2a were increased. In addition, they found that levels of Klf2a overlapped with the levels of Notch.

Further experiments revealed that, when mutated, Trpv4 - a molecule that is known to 'sense' changes in blood flow and can switch on the gene for Klf2a - led to a reduced amount of genes that drive heart cell growth and fewer cells maturing to replace the damaged tissue. Additionally, the team found that changes in blood flow controls heart cell reprogramming and growth via another two molecules, BMP and Erbb2. As these molecules are important for heart regeneration in mammals, the changes observed in the zebrafish may also hold true for other organisms, including humans.

"Our findings show how the heart senses and adaptively responds to environmental changes caused by injury, and provide insight into how flow-mediated mechanisms may regulate heart cell reprogramming and heart regeneration," concludes senior author Neil Chi, Professor of Medicine at UC San Diego. "Future studies are now needed to explore whether blood flow forces may affect mammals such as mice and to reveal new mechanisms that could take us a step towards being able to regenerate the human heart."
-end-
Reference

The paper 'Hemodynamic-mediated endocardial signaling controls in vivo myocardial reprogramming' can be freely accessed online at https://doi.org/10.7554/eLife.44816. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

Media contact

Emily Packer, Senior Press Officer
eLife
e.packer@elifesciences.org
01223 855373

About eLife

eLife aims to help scientists accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours in science. We publish important research in all areas of the life and biomedical sciences, including Developmental Biology, which is selected and evaluated by working scientists and made freely available online without delay. eLife also invests in innovation through open source tool development to accelerate research communication and discovery. Our work is guided by the communities we serve. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, the Wellcome Trust and the Knut and Alice Wallenberg Foundation. Learn more at https://elifesciences.org.

To read the latest Developmental Biology research published in eLife, visit https://elifesciences.org/subjects/developmental-biology.

eLife

Related Blood Flow Articles:

Blood flow recovers faster than brain in micro strokes
Work by a Rice neurobiologist shows that increased blood flow to the brain is not an accurate indicator of neuronal recovery after a microscopic stroke.
Exercise improves memory, boosts blood flow to brain
Scientists have collected plenty of evidence linking exercise to brain health, with some research suggesting fitness may even improve memory.
3D VR blood flow to improve cardiovascular care
Biomedical engineers are developing a massive fluid dynamics simulator that can model blood flow through the full human arterial system at subcellular resolution.
MRI shows blood flow differs in men and women
Healthy men and women have different blood flow characteristics in their hearts, according to a new study.
Brain blood flow sensor discovery could aid treatments for high blood pressure & dementia
A study led by researchers at UCL has discovered the mechanism that allows the brain to monitor its own blood supply, a finding in rats which may help to find new treatments for human conditions including hypertension (high blood pressure) and dementia.
Blood flow monitor could save lives
A tiny fibre-optic sensor has the potential to save lives in open heart surgery, and even during surgery on pre-term babies.
Changes in blood flow tell heart cells to regenerate
Altered blood flow resulting from heart injury switches on a communication cascade that reprograms heart cells and leads to heart regeneration in zebrafish.
Blood flow command center discovered in the brain
An international team of researchers has discovered a group of cells in the brain that may function as a 'master-controller' for the cardiovascular system, orchestrating the control of blood flow to different parts of the body.
Researchers closer to new Alzheimer's therapy with brain blood flow discovery
By discovering the culprit behind decreased blood flow in the brain of people with Alzheimer's, biomedical engineers at Cornell University have made possible promising new therapies for the disease.
In vitro grafts increase blood flow in infarcted rat hearts
Advances in stem cell research offer hope for treatments that could help patients regrow heart muscle tissue after heart attacks, a key to patients achieving more complete recoveries.
More Blood Flow News and Blood Flow 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.