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March 16, 2022

How hypertension turns good fat bad

Vascular fat sounds inherently dangerous, but it can be quite helpful. Maintaining its beneficial purpose is the subject of a Michigan State University study funded with a five-year $13.5 million grant from the National Heart, Lung and Blood Institute at the National Institute of Health.


Perivascular adipose tissue, or PVAT, is a fat that surrounds blood vessels crucial for optimal blood pressure and vascular health. Stephanie Watts, a professor of pharmacology and toxicology in the MSU College of Osteopathic Medicine, leads the grant, which consists of four separate projects and four supportive cores designed to simultaneously study every aspect of PVAT from formation to function.


This integrated work advances human health by redefining what a functional blood vessel is,” Watts said. “A redefinition that could have significant impact on the function and dysfunctions of the body’s vascular system.” 


PVAT is important to the function of the blood vessels because PVAT secretes proteins and lipids that help vessels maintain a normal blood pressure. Healthy PVAT is soft and flexible. When the heart beats, the aorta — the artery that sends blood away from the heart to the rest of the body — moves a little. PVAT cushions this movement and reduces the pressure on the blood vessels.


“Usually, the public thinks fat is bad,” said Andres Contreras, an associate professor in MSU’s College of Veterinary Medicine and one of the project’s lead investigators. “But in this case, healthy perivascular fat is good.”


Hypertension puts extra pressure on the blood vessels, causing PVAT cells to transform from soft adipocyte fat cells to rigid fibroblast scar tissue. Contreras and his team are using two different approaches based on animal models to identify the formation of PVAT and trace the transformation of adipocytes into fibroblasts. The first approach involves putting healthy PVAT cells into a special machine that stretches the surface area of the cells while they are growing to see how the cells respond to the stress if being stretched. The second approach uses a specially designed gel where the researchers can control the firmness of the gel material to pinpoint the moment when a soft fat cell changes into firm scar tissue


“We think the PVAT cells sense the blood vessel’s mechanical forces that are enhanced during hypertension and that increased pressure triggers a change in the fate of those cells,” Contreras said. “The goal is to detect hypertension earlier and maybe find the specific targets inside the cells. If you see this change in the fat around the aorta or a different vessel, does that mean the tissues have started to become stiffer?


Hypertension affects humans, dogs, cats and horses. This study uses animal models which provides multiple opportunities to apply what is learned through this research.


“Given the lack of understanding of the role of PVAT in blood pressure regulation, the use of animal models is still necessary, said Adam Lauver, assistant professor of pharmacology and toxicology in the College of Veterinary Medicine and leader of the animal model core. "The animal core will help improve the efficiency of our research."


“We need to understand both the big picture and what is happening at the cellular level,” Contreras said. “We wouldn’t be able to do it without animal models.” 


While comparable research can take years, concurrent and coordinated experimentation accelerates the research process so its findings can be more rapidly applied.


“This approach (four projects and four cores) is so dynamic,” Contreras said. "It makes the science go so much faster."


Learn more about the four projects and four cores funded by the grant here.

By: Emilie Lorditch

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