Research reveals how blood flow directs vessel health at the molecular level

How do blood vessels stay strong, flexible, and responsive to the body’s changing need for oxygen and nutrients? The answer lies not only in biology—but also in physics. Researchers at Åbo Akademi University and the InFLAMES Flagship have uncovered new molecular pathways that allow blood vessel cells to sense and respond to the mechanical forces generated by blood flow.

The findings, published in iScience and The FEBS Journal, open new possibilities for understanding—and potentially influencing—vascular health in cardiovascular disease, regenerative medicine, and cancer therapy.

A healthy vascular system is vital for life, and cardiovascular disease remains the world’s leading cause of death. Blood vessels are central to tissue function, regeneration, and tumor growth. For example, targeting vessels that supply tumors with nutrients is a powerful strategy in cancer treatment. Understanding how vessels grow, adapt, and maintain stability is therefore a major scientific and clinical priority.

Blood vessels are built of endothelial cells, which line the inside of the vessel and directly contact flowing blood, and contractile mural cells, which surround and support the vessel wall. Together, these cells coordinate vessel strength and growth of new vessels in response to mechanical forces, such as shear stress from blood flow, and signals from surrounding tissues.

At the Cell Fate Lab, led by InFLAMES group leader, Professor Cecilia Sahlgren, researchers investigate how mechanical forces integrate with biological signaling pathways to regulate cardiovascular tissue health and disease.

Previous work from the lab demonstrated that the Jagged1–Notch signaling pathway essential for cardiovascular tissues plays a crucial role in directing vessel growth and stability, enabling neighboring cells to communicate in response to mechanical cues.

In two new studies, the team has now revealed how these physical forces translate into molecular changes inside endothelial cells.

Researchers Noora Virtanen, Kai-Lan Lin, Elmeri Kiviluoto, and postdoctoral scientists Oscar Stassen and Freddy Suarez Rodriguez, under Professor Sahlgren’s supervision, discovered that the molecular motor protein Myo1c is sensitive to shear stress from blood flow. When endothelial cells experience flow, Myo1c releases its cargo protein, Jagged1—precisely controlling where and when signaling occurs within the cell.

This precise delivery system resembles a finely tuned molecular choreography, ensuring that the right signals reach the right location at the right time. Identifying Myo1c as a flow-sensitive motor protein that regulates Jagged1 positioning provides critical insight into how vascular cells control cell signaling under mechanical stress.

The researchers also uncovered an entirely new function of Jagged1. Beyond its well-established role in activating the Notch receptor, Jagged1 can directly trigger force-sensing (mechanotransduction) pathways within endothelial cells.

“While Jagged1 has long been recognized as an important protein in vascular physiology due to its role in activating the Notch receptor, our findings show that its involvement in vascular function extends beyond this classical function. This opens new research avenues and potential therapeutic strategies,” researcher Freddy Suarez Rodriguez explains.

Together, these discoveries deepen our understanding of how blood flow shapes vascular biology at the molecular level—and pave the way for innovative approaches to treating cardiovascular disease, improving regenerative therapies, and targeting tumor blood supply.