Fat around our arteries may play an important role in keeping those blood vessels healthy


A Michigan State University researcher is adding new evidence to the argument that the fat around our arteries may play an important role in keeping those blood vessels healthy.

The finding could affect how researchers test for treatments related to plaque buildup in our arteries, or atherosclerosis, an issue that can often lead to a heart attack, which is currently a leading cause of death in the United States.

The fat, known as perivascular adipose tissue, or PVAT, helps arteries do what scientists call “stress relax,” or let go of muscular tension while under constant strain. This is similar to the bladder, which expands to accommodate more liquid while at the same time keeping it from spilling out.

“In our study, PVAT reduced the tension that blood vessels experience when stretched,” said Stephanie Watts, MSU professor of pharmacology and toxicology in the College of Osteopathic Medicine. “And that’s a good thing, because the vessel then expends less energy. It’s not under as much stress.”

What made the finding so exciting, Watts said, whose study was recently published in the journal Scientific Reports, is that PVAT has largely been ignored by researchers who have thought its main job was to store lipids and do little more.

Now her findings, built on previous results, could help redefine the way scientists view blood vessels.

Right now, scientists only divide blood vessels into three parts, the innermost layer called the tunica intima, the middle layer called the tunica media and the outermost layer called the tunica adventitia.

Watts would like scientists to recognize PVAT as the fourth layer, which others have called tunica adiposa – tunica means a membranous sheath enveloping or lining an organ and adiposa is a synonym for fat.

“For years, we ignored this layer – in the lab it was thrown out; in the clinic it wasn’t imaged. But now we’re discovering it may be integral to our blood vessels,” Watts said.

“Our finding redefines what the functional blood vessels are and is part of what can be dysfunctional in diseases that afflict us, including hypertension.

We need to pay attention to this layer of a blood vessel because it does far more than we originally thought.”

Other investigators have shown that PVAT plays a role in the functioning of blood vessels, finding that it secretes substances that can cause blood vessels to relax as well as substances that can cause it to contract.

But Watts and her colleagues wanted to test whether PVAT itself, rather than the substances it secretes, might play a role in how blood vessels perform.

So, they decided to test whether PVAT provides a structural benefit to arteries by assisting the function of stress relaxation.

To do that, they tested the thoracic aorta in rats and found those with intact PVAT had more stress relaxation than those without.

“My mind was blown,” Watts said when she saw that the pieces with surrounding fat had measurably relaxed more than those without.

“I made every single person in my lab come and look and I asked, ‘Tell me if I’m hallucinating…do you think this is real?'”

Watts and her colleagues also tested other arteries and were able to duplicate the same response.

“So, this tells us, it’s not just a one off,” Watts said. “It’s not something you see only in this particular vessel or this particular species or this particular strain. But that maybe it’s a general phenomenon.”

The adipose tissue of healthy animals contains a large population of innate and adaptive immune cells, numerically dominated by macrophages (Weisberg et al., 2003Xu et al., 2003Lumeng et al., 2007).

The functions of these cells in the healthy adipose tissue of animals in steady state are not completely understood. The proportions and numbers of these immune cell types are known to change extensively in conditions such as diet-induced obesity (DIO), genetically determined obesity, and aging, among other situations.

It has been long known that obesity is associated with a heightened inflammatory condition, in which TNFα is an important mediator of insulin resistance (Feinstein et al., 1993Hotamisligil et al., 19931995).

It has been postulated that the myeloid cells found in the adipose tissue during DIO contribute to the pathogenesis of insulin resistance and the metabolic syndrome by increasing their secretion of proinflammatory cytokines (Dalmas et al., 2011Lumeng, 2013Wynn et al., 2013Xu et al., 2013Fitzgibbons and Czech, 2016Alemán et al., 2017).

High-fat diet (HFD) induces obesity and insulin resistance in B6 mice (Surwit et al., 1988Rebuffé-Scrive et al., 1993). Adipocytes become hypertrophic, which could be the initial signal to trigger inflammation (Sun et al., 2011Rutkowski et al., 2015); however, cultured adipocytes made hypertrophic with oleic acid display insulin resistance without triggering an inflammatory response (Kim et al., 2015).

Thus, the role of the inflammatory response in obesity-related disease is not clearly established. Moreover, wild animals endure fluctuations in food supply, in which the adipose tissue triglyceride reserves are mobilized via lipolysis or built from the diet, and little is known about the response of immune cells to these fluctuations.

In this report, we found that tissue-resident macrophages from healthy epididymal white adipose tissue (eWAT), a visceral fat depot, not only surround adipocytes but also associate tightly with blood vessels, being among the most endocytic cells in the body for blood-borne macromolecules.

We refer to these macrophages as vasculature-associated adipose tissue macrophages (VAMs). Upon chronic HFD feeding, a monocyte-derived CD11c+CD64+ double-positive (DP) population of macrophages, poorly represented in animals fed a normal diet (ND), surges in the eWAT. Contrary to some predictions, these macrophages have predominantly an anti-inflammatory and repair gene signature.

Importantly, eWAT macrophages from HFD-fed mice have a reduced endocytic capacity. Differently, a brief fasting period rapidly and reversibly reduces all macrophage populations, especially VAMs. Acute systemic inflammatory stress, such as that induced by LPS administration or Salmonella enterica serovar Typhimurium infection, results in a rapid and transient reduction in the main populations of VAMs; however, in this case, the decrease in VAMs is accompanied by an increase in DP macrophages.

Taken all together, the macrophage populations dynamically adapt to metabolic stress and inflammation by adjusting their numbers and the expression of beneficial genes, even when pathology ends up prevailing.

More information: Stephanie W. Watts et al, A New Function for Perivascular Adipose Tissue (PVAT): Assistance of Arterial Stress Relaxation, Scientific Reports (2020). DOI: 10.1038/s41598-020-58368-x


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