Blood vessels found to be key to cardiovascular disease: study

Cardiovascular disease is responsible for roughly a third of all deaths in developed countries—but new research suggest we may be looking at it the wrong way. While heart attacks and strokes are often seen as conditions affecting the heart and brain, experts now point to blood vessels as the underlying cause.

For years, vascular endothelial cells, which line the inner surfaces of blood vessels, were considered passive responders, merely reacting to environmental cues such as inflammation or cytokines that induce angiogenesis.

“This conceptual view isn’t wrong, but it’s too reductionist,” said Dr. Koh Gou-young, director of the Center for Vascular at the Institute for Basic Science (IBS) and professor at Korea Advanced Insittute of Science and Technology’s (KAIST) Graduate School of Medical Science and Engineering. 

In a new study published last Friday in the biology journal Cell, Koh and his long-time research partner, Professor Hellmut G. Augustin from the European Center for Angioscience (ECAS) at Heidelberg University, challenge this outdated perspective.

“We posit that blood vessels should be considered a systemically disseminated organ,” the two researchers said. Their research overturned the notion that blood vessels are mere passive conduits, revealing them as crucial organs essential to development and regeneration, and "critically involved in almost every major life-threatening and chronic human disease"

Blood vessels revealed as key factors in heart disease, cancer, and aging

Cardiac diseases, long recognized for their devastating toll, are often misunderstood in their origins. While the heart gets the blame, the real culprit lies in the blood vessels that power it. 

For instance, cardiac ischemia—typically classified as a heart issue—is actually a vascular problem that starves the heart of oxygen. Similarly, ischemic strokes, which disrupt brain function, are also rooted in the vasculature.

Vascular aging, once linked to hardened arteries, has an equally dangerous counterpart at the microscopic level. As we age, the signaling for vascular endothelial growth factor (VEGF)—a molecule essential for maintaining blood vessels—weakens. This decline leads to the loss of small blood vessels, contributing to a various age-related diseases.

But the impact of blood vessels doesn’t stop there. They also play a pivotal role in cancer progression.

Tumors, notorious for their deadly growth, rely on blood vessels to survive. Without the support of new vessels, a tumor can't grow beyond a microscopic size. Blood vessles also enable metastasis, the spread of cancer to distant organs—a leading cause of cancer deaths. Inflammatory diseases also have blood vessels at their core, as endothelial cells lining these vessels regulate the body’s inflammatory responses, controlling the movement of white blood cells.

Koh also warned of a deeper connection between endothelial cell dysfunction and chronic diseases like diabetes, obesity, and dementia. Once endothelial cells fail to function properly, they accelerate the development of these debilitating conditions. The reach of this dysfunction extends to eye diseases, contributing to blindness in millions, and is also tied to metabolic syndrome, arthritis, and cognitive decline.

The study also uncovered the molecular diversity of endothelial cells at a single-cell level, revealing that these cells are far from uniform. Depending on the organ and blood vessel type, endothelial cells perform highly specialized roles. 

In the brain and muscles, they form protective barriers; in the kidneys, they act as vital filters. In the liver, endothelial cells regulate metabolic differentiation and contribute to hepatocyte regeneration, demonstrating their crucial roles across different bodily systems.

Koh called for a “new wave of therapeutic strategies focusing on vascular endothelial cells,” highlighting the potential of regenerative medicine, rehabilitation, and the prevention and repair of vascular aging as promising areas for clinical innovation. 

The full study detailing these findings can be found in the biology journal, Cell.