SAN DIEGO — One-third of global deaths are due to cardiovascular disease caused by atherosclerosis, when arteries are clogged with fat deposits. Although it’s common for humans to experience heart attacks, the same event is rare in mammals. Now, researchers believe that they understand why.
Risk factors for cardiovascular disease in humans can include age, hypertension, obesity, smoking, blood cholesterol and inactivity. However, in 15% of cardiovascular events caused by atherosclerosis, none of these risk factors is at hand.
Closely related mammals like chimpanzees living in captivity share some of the same risk factors for cardiovascular disease: hypertension, inactivity and high blood lipids. But these chimps rarely experience heart attacks. If they do, it’s not due to atherosclerosis; the cause is scarring of the heart muscle, which has yet to be explained.
Researchers think that there was the loss of a single gene, CMAH, in human ancestors between 2 million and 3 million years ago, leading to a higher risk of cardiovascular disease. This gene included a sialic acid sugar molecule called Neu5Gc. Apes and chimps have maintained this gene and molecule over time.
In a new study, mice were modified to be similarly deficient in this molecule, which caused a twofold increase in atherosclerosis compared with mice who were not modified. The study was published Monday in the journal Proceedings of the National Academy of Science.
“The increased risk appears to be driven by multiple factors, including hyperactive white cells and a tendency to diabetes in the human-like mice,” said study author Dr. Ajit Varki, Distinguished Professor of Medicine and Cellular and Molecular Medicine at the University of California San Diego School of Medicine. “This may help explain why even vegetarian humans without any other obvious cardiovascular risk factors are still very prone to heart attacks and strokes, while other evolutionary relatives are not.”
Even though humans lack this gene and the Neu5Gc molecule within it, those who regularly eat red meat are exposed to it. Consuming it as a byproduct of red meat causes the human body to react with an immune response as well as chronic inflammation. The modified mice in the study were fed a diet similar to that of humans who eat red meat: high in fat and rich in Neu5Gc. This caused the mice to develop an additional 2.4-fold increase in atherosclerosis.
“The human evolutionary loss of CMAH likely contributes to a predisposition to atherosclerosis by both intrinsic and extrinsic [dietary] factors and future studies could consider using this more human-like model,” the study authors wrote.
The same research team has also demonstrated that modified mice fed a Neu5Gc-rich diet were more susceptible to inflammation and cancer progression, suggesting a link between certain cancers and diets rich in red meat.