The body’s ability to grow new blood vessels is vital for helping wounds heal, maintaining a healthy pregnancy, supporting muscle growth, and more.
Like many cellular processes, however, there’s a Goldilocks zone for angiogenesis.
“Balance is key,” said Dr. Charles Thodeti, a professor in The University of Toledo College of Medicine and Life Sciences. “Too much angiogenesis can fuel tumors or damage the retina in diseases like diabetic retinopathy. On the flip side, too little can block blood flow in heart disease or stroke. It’s a critical process but when it goes haywire, it can become dangerous.”
Dr. Charles Thodeti, professor in the College of Medicine and Life Sciences, recently received a $300,000 research grant from the American Heart Association to study how mechanical forces encourage the growth of new blood vessels.
With a three-year, $300,000 grant from the American Heart Association, Thodeti is leading new research that takes an unconventional look at what drives angiogenesis — and how that process could potentially be manipulated to address a variety of diseases and conditions.
New blood vessels sprout out from existing ones in response to cellular signals they receive. It’s a fundamental biological process, and one that has significant implications in overall health.
It’s also something that scientists still don’t fully understand.
“There are a lot of people working on this idea but they’re all looking at it in essentially the same way, starting with the chemical signals that stimulate the formation of new blood vessels,” Thodeti said. “My take is totally different.”
Rather than looking at proteins suspended in the blood, he’s studying the motion of the blood itself.
As blood flows through our body, it puts physical pressure on the cells that line our blood vessels. Increasingly, researchers like Thodeti are recognizing that force helps encourage the formation of new blood vessels.
A breakthrough for his lab came with their discovery that a molecule called TRPV4 plays a key role in angiogenesis by not only helping cells sense those mechanical forces but also influencing how they respond by sending signals to their mitochondria.
With the new American Heart Association Transformational Project Award, he and his colleagues aim to deepen their understanding of exactly how mechanical signaling regulates mitochondrial metabolism and in turn, how it controls angiogenesis.
The hope, Thodeti said, is that the new knowledge might allow for more specific and effective interventions that could starve out cancers or bring more oxygen-rich blood to damaged tissue.
His prior work has already shown that TRPV4 can act as a brake, keeping angiogenesis in check. They’ve also identified a protein that seems to serve as the conduit between TRPV4 and the mitochondria, giving them a potential therapeutic target.
“By linking mechanical force, energy metabolism and blood vessel biology, we’re building a new roadmap for treating tough diseases, where current drugs just don’t cut it,” Thodeti said. “We are really optimistic about the potential impact this could have on some of the most common and most deadly diseases.”
Thodeti’s research team includes postdoctoral fellows Dr. Venkatesh Katari and Dr. Narendra Kondapalli and doctoral student Kesha Dalal.