Evolutionary gene loss may explain the increased risk of cardiovascular disease in humans

Researchers at the University of California San Diego School of Medicine claim that the loss of a single gene two or three million years ago in our ancestors could have resulted in increased risk cardiovascular disease in all humans, while creating additional risk. for humans eating red meat. The results are published on 22 July 2019 in PNAS.

Atherosclerosis – clogging arteries with fatty deposits is the cause of a third of the world's deaths due to cardiovascular disease. There are many known risk factors, including blood cholesterol, physical inactivity, age, hypertension, obesity and smoking, but in about 15% of the first cases Cardiovascular disease (CVD) due to atherosclerosis, none of these factors apply.

Ten years ago, Nissi Varki, MD, professor of pathology at the UC Medical School in San Diego, with co-author Ajit Varki, MD, Distinguished Professor of Medicine and Cellular and Molecular Medicine , and colleagues noted that natural coronary heart attacks atherosclerosis is virtually non-existent in other mammals, including closely related captive chimpanzees that share risk factors similar to those of humans. , such as high blood lipids, high blood pressure and physical inactivity. Instead, the "heart attacks" of chimpanzees were due to an unexplained scar of the heart muscle.

In the new study, Varkis and Philip Gordts, Ph.D., badistant professor of medicine, and others report that mice modified to be deficient (like humans) into a sugar molecule. sialic acid called Neu5Gc showed a significant increase in atherogenesis compared to control mice. , which retain the CMAH gene that produces Neu5Gc.

Researchers, members of the Center for Research and Training in Glycobiology and / or the Center for University Research and Training in Anthropology at the University of San Diego, believe that a mutation that inactivated the CMAH gene s & dquo; Was produced a few million years ago in ancestors of hominins, event possibly related to a malaria parasite that recognized Neu5Gc.

In their conclusions, the research team stated that human elimination of both CMAH and Neu5Gc in mice resulted in atherosclerosis at almost twice the severity of unmodified mice.

"The increased risk seems to result from multiple factors, including hyperactive white blood cells and a tendency to diabetes in human-type mice," said Ajit Varki. "This may help explain why even vegetarian humans without any obvious cardiovascular risk factors are still very prone to heart attacks and strokes, while other evolutionary parents are not."

But by consuming red meat, humans are also repeatedly exposed to Neu5Gc, which, according to the researchers, causes an immune response and chronic inflammation that they call "xenosialitis". During their tests, human-type mice modified to no longer have the CMAH gene were fed a diet rich in Neu5Gc and subsequently underwent an increase in atherosclerosis twice as large, which could be explained by changes in fats or sugars in the blood.

"The loss of CMAH in human evolution is likely contributing to a predisposition to atherosclerosis by intrinsic and extrinsic (dietary) factors," the authors wrote, "and future studies might consider d & # 39; use this more human model. "

In earlier work, Varkis and colleagues have shown that Neu5Gc feeding also promotes progression of inflammation and cancer in Neu5Gc-deficient mice, suggesting that the non-human sugar molecule, which is abundant in red meat, can at least partly explain the link between consumption of red meat and certain cancers.

Interestingly, the progressive loss of the CMAH gene appears to have led to other important changes in human physiology, including reduced fertility and increased ability to run long distances.