Why humans are more likely to die of a heart attack than animals

Millions of years ago a genetic mutation in humans would have made them much more vulnerable to atherosclerosis, responsible for a third of deaths from cardiovascular disease.

Atherosclerosis is characterized by the deposition of a plaque essentially composed of lipids on the walls of the arteries. Ultimately, these plaques can cause damage to the arterial wall, lead to obstruction of the vessel or rupture. Thus, atherosclerosis is responsible for a third of deaths from cardiovascular diseases.

Many known risk factors, such as physical inactivity, age, hypertension, obesity and smoking, account for about 15% of atherosclerotic cardiovascular problems. According to a study published on July 22 in the journal PNASthis could be due to the loss of a gene in humans two or three million years ago. And the big consumers of red meat are even more at risk, the researchers note.

About ten years ago, scientists at the University of San Diego Medical School had noticed that heart attacks from atherosclerosis did not exist in other mammals, even among our cousins, chimpanzees. . And yet, those studied shared risk factors common to humans such as hypertension and physical inactivity. In conclusion, the researchers noted that the animal heart attacks were due to a scar of the unexplained heart muscle.

Elimination of the CMAH gene

Based on these results, they decided to work today on mice that they modified by removing, like humans, the CMAH gene that produces a sugar molecule called Neu5Gc. They then observed that the modified rodents showed a significant increase in atherogenesis, which produces atheroma, plaques consisting of lipids attaching to the inner lining of the arteries, compared to mice in the control group. As a result, the elimination of the CMAH gene resulted in atherosclerosis severity almost twice that of unmodified animals.

Thus, the mutation that deactivated the CMAH gene would have occurred several million years ago in our hominid ancestors, possibly because of a parasite that recognizes Neu5Gc, say the researchers.

"The increased risk seems to be caused by many factors, including hyperactive white blood cells and a tendency to diabetes in modified mice," says Ajit Varki, co-author of the study. "This could help explain why even vegetarian humans without obvious cardiovascular risks are still very likely to have heart attacks and attacks, unlike other animal species."

Fat lovers of red meat more at risk

However, fat red meat enthusiasts remain more exposed to Neu5Gc, which has an immune response and causes chronic inflammation. In fact, during the study, the modified mice subjected to a diet rich in Neu5Gc suffered from 2.4 times more atherosclerosis. "The loss of CMAH in human evolution probably contributes to a predisposition to atherosclerosis by intrinsic and extrinsic (food) factors," the researchers conclude.

In the past, they had already shown that the diet rich in Neu5Gc also promoted inflammation and cancer in mice that did not have this molecule. Thus, the non-human sugar molecule, abundant in red meat, could partly explain a link between its consumption and certain cancers. In addition to cardiovascular disease and cancer, the progressive loss of human CAME also appears to have reduced fertility or increased ability to travel long distances.

But while cardiovascular problems are much more common in humans, animals are not completely spared. Thus, thousands of dogs around the world die each year from a heart attack. In addition to atherosclerosis, the problem can occur if the animal has bacterial infection, nephrotic syndrome, hypothyroidism, tumor or vasculitis.

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