The Hidden Role of Blood Flow in Heart Health
Blood flow influences heart and vessel health more than we realized.
Freddy Suarez Rodriguez, Noora Virtanen, Elmeri Kiviluoto, Rob C. H. Driessen, Feihu Zhao, Carlijn V. C. Bouten, Oscar M. J. A. Stassen, Cecilia M. Sahlgren
― 7 min read
Table of Contents
- What is Shear Stress?
- The Role of Endothelial Cells
- Pressure Makes a Difference
- What’s the Notch Signaling Pathway?
- The Tug-of-War of Jagged1
- Impact of Different Blood Flow Levels
- Jagged1 and Endothelial Cell Behavior
- The Impact of Silencing Jagged1
- Mechanical Forces and Kinase Activity
- The Relationship with VEGFR2
- The Mystery of Notch Inhibitors
- Jagged1 in Zebrafish
- The Role of ERK
- The Importance of Study
- Future Directions
- Final Thoughts
- Original Source
Blood is not just a red liquid; it has a job to do. Among its many tasks, blood flow plays a key role in shaping our heart and blood vessels. This process is called cardiovascular morphogenesis. When blood flows through our vessels, it creates forces that can influence how these vessels develop, maintain their structure, and how diseases like atherosclerosis can start or progress.
What is Shear Stress?
When blood flows, it doesn’t just move in a straight line like a calm river. Instead, it creates what's known as "Fluid Shear Stress" (FSS). This FSS is a fancy way of saying that blood flow pushes against the walls of our blood vessels. Endothelial Cells, which are the cells lining our blood vessels, sense this stress. It’s kind of like how you might feel the wind pushing against you when you walk outside. These cells need to respond to that push to keep our blood vessels healthy.
The Role of Endothelial Cells
Endothelial cells are like the bodyguards of your blood vessels. They need to be aware of the changing forces of blood flow. When blood flows smoothly, it's good for these cells and helps them stay healthy. But when the flow isn’t smooth, or if it's really weak, that can lead to trouble. Areas with weak blood flow are more likely to develop blockages or plaques, like a sink getting clogged. These plaques can eventually lead to serious diseases like heart attacks.
Pressure Makes a Difference
Different blood vessels experience different amounts of pressure from the blood flowing through them. The pressure can range from super low (like a barely dripping faucet) to pretty high (like a strong fire hose). Endothelial cells react differently depending on how much pressure they feel. Some of them might get alarmed and start reacting to the flow, while others might just chill out.
Notch Signaling Pathway?
What’s theNow let’s talk about a helper that endothelial cells have: the Notch signaling pathway. It's essential for keeping our cardiovascular system in shape. Think of it as a communication line between cells. When certain signals come through, cells know when to grow, when to repair, and how to behave in general.
Notch signaling is pretty nifty. When cells send out a signal, it binds to Notch proteins on the neighboring cells. This binding tells the neighboring cells to act a certain way, keeping everything in balance. If the signaling is off, it can lead to problems in our blood vessels and heart.
The Tug-of-War of Jagged1
Here enters Jagged1, a special protein that interacts with the Notch pathway. But don’t let the name fool you; it's not just a jagged edge. It plays a significant role in blood vessel health.
When blood flows strongly, it can encourage Jagged1 to activate, which helps support the structure of blood vessels. However, in areas where the blood flow is weak, Jagged1 can get a bit too cozy and promote the formation of plaques. So, it’s kind of like having a friend who can either be a great help or the life of the party that gets out of hand!
Impact of Different Blood Flow Levels
Scientists have been measuring how different levels of blood flow can influence Jagged1 and its behavior. The more they study it, the more they find out that not all blood flows are equal. In areas with strong, smooth flow, Jagged1 behaves itself and helps keep things in order. But in areas with weaker flow, it can start causing issues, which is a bit of a double-edged sword.
Jagged1 and Endothelial Cell Behavior
To better understand how Jagged1 behaves with different blood flows, researchers put endothelial cells under various flow conditions. It was discovered that when exposed to a steady flow, Jagged1 moved around in the cells and even started to cluster together in specific areas. This kind of behavior means that Jagged1 is responding to changes in flow, which can influence how well endothelial cells function.
The Impact of Silencing Jagged1
When researchers silenced Jagged1 in experiments, they noticed that some signaling pathways related to blood flow were affected. Without Jagged1, the endothelial cells didn’t activate the same pathways that help regulate blood vessel function. This suggests that Jagged1 is playing an important role in helping cells respond to changes in blood flow.
Mechanical Forces and Kinase Activity
But there's more! The researchers wanted to see if by applying physical forces to Jagged1, they could stimulate certain activities in the cells. They cleverly attached tiny magnetic beads to Jagged1, then used magnets to pull on these beads. This tugging seemed to activate specific signaling pathways in the cells, which was a clear indication that the physical pressure could influence how cells behave.
The Relationship with VEGFR2
The experiments also pointed out another protein called VEGFR2. This protein is essential for blood vessel growth and health. When Jagged1 was pulled with those magnetic beads, it activated VEGFR2, which means it was helping cells communicate important messages. This communication helps endothelial cells grow and maintain their structure.
The Mystery of Notch Inhibitors
Interestingly, when researchers blocked the Notch pathway in cells, they found that Jagged1 could still activate VEGFR2. This indicates that Jagged1 has a life of its own and doesn't always work through Notch signaling. It suggests that Jagged1 might have some hidden talents that go beyond what scientists previously thought.
Jagged1 in Zebrafish
To see how Jagged1 works in real life, researchers turned to zebrafish. These little creatures are great for studying because of their transparent bodies and rapid development. By knocking out Jagged1 in zebrafish, they observed some interesting changes. The fish displayed signs of cardiac edema, which is like swelling in the heart area. This indicated that Jagged1 was important for heart health, and its absence led to complications.
The Role of ERK
As they examined Jagged1-deficient zebrafish, researchers looked at another important player: ERK. ERK is a signaling molecule that helps control a variety of cellular processes. When Jagged1 was missing, the activity of ERK was reduced. This finding aligns with the idea that Jagged1 is a key player in heart development and that its absence can lead to significant health issues.
The Importance of Study
In conclusion, this research shines a light on how blood flow and specific proteins like Jagged1 and Notch work together to maintain cardiovascular health. It's all about the balance of signals in the body. If one part goes awry, it can lead to bigger issues down the line, just like a domino effect. So next time you think about blood, remember: it's not just pumping through your veins. It's also actively shaping your health and well-being, one beat at a time!
Future Directions
This study opens up new avenues for understanding cardiovascular diseases. By focusing on Jagged1's roles outside of traditional Notch signaling, researchers can delve deeper into how these proteins interact with blood flow. Understanding these relationships may lead to improved treatments and therapies for heart diseases.
Final Thoughts
So, stay tuned, folks! The world of blood flow and heart health is full of surprises. Who knew such tiny components could have such big effects? Just goes to show you, in the complex world of biology, even the tiniest players can take center stage!
Title: Jagged1 is a Notch-independent mechanotransducer in endothelial cells
Abstract: Fluid shear stress (FSS) from the blood flow is a crucial regulator of vascular physiology and is associated with major cardiovascular pathologies. Endothelial cells are the primary mechanotransducers of FSS. Here, we show that Jagged1, a canonical ligand of the Notch pathway, modulates biomechanical signaling in endothelial cells in response to FSS. We found that changes in FSS magnitude alter the expression and localization of Jagged1 independently of its effect on Notch expression or activation. Deletion of Jagged1 decreases FSS-induced VEGFR2 and ERK activity in vitro and causes attenuated kinase activity and cardiac defects in zebrafish embryos without significant changes in canonical Notch activity. We show that direct physical stimulation of Jagged1 induces mechanosignaling through the VEGFR2 pathway, independently of Notch signaling but mediated by Jagged1-induced Src activation. Our findings suggest a novel non-canonical role for Jagged1 as a mechanotransducer in endothelial cells with implications for cardiovascular morphogenesis and disease. One Sentence SummaryJag1 activates endothelial mechanosignaling through Src.
Authors: Freddy Suarez Rodriguez, Noora Virtanen, Elmeri Kiviluoto, Rob C. H. Driessen, Feihu Zhao, Carlijn V. C. Bouten, Oscar M. J. A. Stassen, Cecilia M. Sahlgren
Last Update: 2024-11-15 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.14.623558
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.14.623558.full.pdf
Licence: https://creativecommons.org/licenses/by/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.