Researchers at the University of Pittsburgh School of Medicine have discovered a molecular mechanism by which excess dietary protein may increase the risk of atherosclerosis. The results were published Nature Metabolism today

The study, which combined small human experiments with experiments on mice and cells in a petri dish, showed that consuming more than 22 percent of dietary calories from protein led to an increase in immune cell activity that prevented atherosclerotic plaque. play a role in the formation, which drives the disease. Risk Additionally, the scientists showed that one amino acid — leucine — has a disproportionate role in driving the pathological pathways associated with atherosclerosis, or hardened, hardened arteries.

“Our study shows that dialing down your protein intake to achieve better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, MD, Ph.D. D, said the professor. of Cardiology at Pitt. “Our hope is that this research will start a conversation about ways to modify diet that can affect body function at a molecular level and reduce disease risks.”

According to the Average American Diet Survey over the past decade, Americans generally eat a lot of protein, mostly from animal sources. Additionally, about a quarter of the population gets 22 percent of their total daily calories from protein alone.

Razani says this trend is likely driven by the popular belief that dietary protein is essential for a healthy life. But he and other groups have shown that overreliance on protein is not such a good thing for long-term health.

Following their 2020 study, in which Razani’s lab showed for the first time that high dietary protein increased the risk of atherosclerosis in mice, their next study, conducted by Bettina Mittendorff, a metabolist at the University of Missouri in Columbia, P. In collaboration with HD, further in-depth research was carried out. A possible mechanism and its relevance to the human body.

To reach the answer, Razani’s laboratory, led by first authors Xiangyu Zhang, Ph.D., and Divya Kapoor, MD, combined their expertise in cellular biology and metabolism with Mittendorfer’s group and A series of different experiments were carried out. Models — from cells to mice to humans.

“We’ve shown in our mechanistic studies that amino acids, which are really the building blocks of proteins, can trigger disease through specific signaling mechanisms and then also change the metabolism of these cells,” Mittendorfer said. ” “For example, tiny immune cells in the vasculature called macrophages can stimulate the development of atherosclerosis.”

Based on preliminary experiments in healthy human subjects, to determine the timeline of immune cell activation following consumption of protein-rich foods, the researchers isolated, in mouse and human macrophages, immune cells that are particularly sensitive to amino acids. Apparently, I simulated similar situations. Protein

Their work shows that consuming more than 22 percent of daily dietary calories from protein can negatively affect macrophages, which are responsible for cleaning up cellular debris, resulting in plaque within the vessel walls. A “graveyard” of these cells accumulates and overtime the atherosclerotic plaques deteriorate. . Interestingly, analysis of circulating amino acids shows that leucine — an amino acid that is enriched in animal-derived foods such as beef, eggs, and milk — is primarily non-essential. is responsible for modest macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalization. Diet modification, or “health nutrition.”

Razani cautions that many questions remain unanswered, primarily: What happens when a person consumes between the USDA’s recommended 15% of daily calories from protein and 22% of daily calories from protein? does, and if someone’s sweet spot’ to maximize the benefits of protein — such as muscle gain — while avoiding kick-starting the molecular cascade of harmful events that lead to heart disease. .

These findings are particularly relevant in hospital settings, where nutritionists often recommend a protein-rich diet for critically ill patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said. “Instead, it’s important to look at the diet as a whole and recommend balanced meals that don’t inadvertently worsen cardiovascular conditions, especially in those at risk for heart disease and arteriosclerosis. “

Razani also noted that these findings suggest differences in leucine levels between diets rich in plant and animal proteins may explain differences in their effects on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is exciting,” he said.

Additional study authors include Yu-Sheng Yeh, Ph.D. are, who are also from Pitt. Alan Fappi, Ph.D., and Wasavi Shabrish, Ph.D., both of the University of Missouri, Columbia; Se-Jin Jeong, Ph.D., Jeremiah Stitham, MD, Ph.D., Ismail Sergin, Ph.D., Eman Yousif, MD, Astrid Rodriguez-Velez, Ph.D., Arick Park, MD, Ph.D. d. D., Joel Schilling, MD, PhD, Marco Sardello, PhD, Abhino Dewan, MD, Nathan Stezel, MD, PhD, Ali Johari, MD, PhD, Irfan Lodhi, P. H.D., and Jaehyung Cho, Ph.D., all of Washington University School of Medicine, St. Louis; Arif Yerdagul Jr., Ph.D., and Oren Rom, Ph.D., both of Louisiana State University Health Sciences Center; and Slava Appleman, MD, PhD, of the University of Toronto.