Scientists Discover How Blood Flow Patterns Trigger Artery Disease Through Enzyme Switch

This groundbreaking research explains how blood flow patterns directly influence artery health at the molecular level, offering new insights into preventing cardiovascular disease. Understanding this mechanism could lead to targeted therapies for atherosclerosis, a leading cause of heart attacks and strokes.

Researchers studied how oscillatory shear stress from disturbed blood flow affects endothelial cells lining arteries. They used multiple approaches including genome analysis, mass spectrometry, and genetically modified mice to trace the complete molecular pathway.

The team discovered that disturbed flow reduces KLF2, a protective protein that normally suppresses DAPK2. When DAPK2 increases, it phosphorylates PKM2 at a specific site, causing PKM2 to form dimers and migrate to cell nuclei. Nuclear PKM2 then activates inflammatory genes like VCAM-1 and ICAM-1, promoting atherosclerosis. Mice lacking endothelial DAPK2 showed dramatically reduced plaque formation.

This pathway represents a direct link between mechanical forces and genetic responses in blood vessels. The findings suggest that targeting DAPK2 or preventing PKM2 phosphorylation could protect against atherosclerosis. Since disturbed flow occurs naturally at artery branch points and curves, this mechanism helps explain why plaques develop in predictable locations. The research also validates PKM2 phosphorylation as a potential biomarker for cardiovascular risk assessment and therapeutic monitoring.