Eating too much protein is bad for your arteries, and this amino acid is to blame

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University of Pittsburgh School of Medicine researchers discovered a molecular system by which excessive dietary macromolecule could summation atherosclerosis risk. The findings were published successful Nature Metabolism today.

The study, which mixed mini quality tests pinch experiments successful mice and cells successful a Petri dish, showed that consuming complete 22% of dietary calories from macromolecule tin lead to accrued activation of immune cells that play a domiciled successful atherosclerotic plaque formation, driving nan illness risk. Furthermore, nan scientists showed that 1 amino acerb -- leucine -- seems to person a disproportionate domiciled successful driving nan pathological pathways linked to atherosclerosis, aliases stiff, hardened arteries.

"Our study shows that dialing up your macromolecule intake successful pursuit of amended metabolic wellness is not a panacea. You could beryllium doing existent harm to your arteries," said elder and co-corresponding writer Babak Razani, M.D., Ph.D., professor of cardiology astatine Pitt. "Our dream is that this investigation starts a speech astir ways of modifying diets successful a precise mode that tin power assemblage usability astatine a molecular level and dampen illness risks."

According to a study of an mean American fare complete nan past decade, Americans mostly devour a batch of protein, mostly from animal sources. Further, astir a 4th of nan organization receives complete 22% of each regular calories from macromolecule alone.

That inclination is apt driven by nan celebrated thought that dietary macromolecule is basal to patient living, says Razani. But his and different groups person shown that overreliance connected macromolecule whitethorn not beryllium specified a bully point for semipermanent health.

Following their 2020 research, successful which Razani's laboratory first showed that excess dietary macromolecule increases atherosclerosis consequence successful mice, his adjacent study successful collaboration pinch Bettina Mittendorfer, Ph.D., a metabolism master astatine nan University of Missouri, Columbia, delved deeper into nan imaginable system and its relevance to nan quality body.

To get astatine nan answer, Razani's laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up pinch Mittendorfer's group to harvester their expertise successful cellular biology and metabolism and execute a bid of experiments crossed various models -- from cells to mice to humans.

"We person shown successful our mechanistic studies that amino acids, which are really nan building blocks of nan protein, tin trigger illness done circumstantial signaling mechanisms and past besides change nan metabolism of these cells," Mittendorfer said. "For instance, mini immune cells successful nan vasculature called macrophages tin trigger nan improvement of atherosclerosis."

Based connected first experiments successful patient quality subjects to find nan timeline of immune compartment activation pursuing ingestion of protein-enriched meals, nan researchers simulated akin conditions successful mice and successful quality macrophages, immune cells that are shown to beryllium peculiarly delicate to amino acids derived from protein.

Their activity showed that consuming much than 22% of regular dietary calories done macromolecule tin negatively impact macrophages that are responsible for clearing retired cellular debris, starring to nan accumulation of a "graveyard" of those cells wrong nan alloy walls and worsening of atherosclerotic plaques overtime. Interestingly, nan study of circulating amino acids showed that leucine -- an amino acerb enriched successful animal-derived foods for illustration beef, eggs and beverage -- is chiefly responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a imaginable avenue for further investigation connected personalized fare modification, aliases "precision nutrition."

Razani is observant to statement that galore questions stay to beryllium answered, mainly: What happens erstwhile a personification consumes betwixt 15% of regular calories from macromolecule arsenic recommended by nan USDA and 22% of regular calories from protein, and if location is simply a 'sweet spot' for maximizing nan benefits of macromolecule -- specified arsenic musculus summation -- while avoiding kick-starting a molecular cascade of damaging events starring to cardiovascular disease.

The findings are peculiarly applicable successful infirmary settings, wherever nutritionists often urge protein-rich foods for nan sickest patients to sphere musculus wide and strength.

"Perhaps blindly expanding macromolecule load is wrong," Razani said. "Instead, it's important to look astatine nan fare arsenic a full and propose balanced meals that won't inadvertently exacerbate cardiovascular conditions, particularly successful group astatine consequence of bosom illness and alloy disorders."

Razani besides notes that these findings propose differences successful leucine levels betwixt diets enriched successful works and animal macromolecule mightiness explicate nan differences successful their effect connected cardiovascular and metabolic health. "The imaginable for this type of mechanistic investigation to pass early dietary guidelines is rather exciting," he said.

Additional authors of nan study are Yu-Sheng Yeh, Ph.D., besides from Pitt; Alan Fappi, Ph.D. and Vasavi Shabrish, Ph.D., some of nan University of Missouri, Columbia; Se-Jin Jeong, Ph.D., Jeremiah Stitham, M.D., Ph.D., Ismail Sergin, Ph.D., Eman Yousif, M.D., Astrid Rodriguez-Velez, Ph.D., Arick Park, M.D., Ph.D., Joel Schilling, M.D., Ph.D., Marco Sardiello, Ph.D., Abhinav Diwan, M.D., Nathan Stitziel, M.D., Ph.D., Ali Javaheri, M.D., Ph.D., Irfan Lodhi, Ph.D., and Jaehyung Cho, Ph.D., each of Washington University School of Medicine, St. Louis; Arif Yurdagul Jr, Ph.D., and Oren Rom, Ph.D., some of nan Louisiana State University Health Sciences Center; and Slava Epelman, M.D., Ph.D., of nan University of Toronto.