Evolutionary Gene Loss May Explain Why Only Humans Have Heart Attacks

(CN) – Humans and captive chimps both consume red meat and live fairly sedentary lifestyles, but only the former develops a plaque buildup in their arteries. Research published in Proceedings of the National Academy of Sciences on Monday pinpoints a missing gene that may make humans more susceptible to heart disease than our jungle-swinging cousins.

Cardiovascular health is one of many factors altered by the loss of the CMAH gene, an event researchers at University of California, San Diego, School of Medicine describe as “the first reported clear-cut difference at the genetic and molecular level between humans and chimpanzees.”

Heart disease is the greatest cause of death worldwide, with 17.9 million cases annually. Fifteen percent of first-time heart disease victims are free of the usual lifestyle red flags like being overweight, smoking, or eating red meat. Overall, atherosclerosis – the buildup of plaque on artery walls – is almost uniquely a human disease and is a leading cause of heart attacks and strokes.

Some might be quick to point to human’s diet – heavy in processed foods – as the culprit, but researchers cite ancient mummies who died from similar causes thousands of years before the first Twinkie was ever manufactured. Captive chimpanzees, which have a sedentary lifestyle similar to those of modern westerners, also do not develop the same heart problems common among humans. In nature, no other animal develops atherosclerosis.

While diet and exercise are certainly contributing factors, they don’t paint a picture of cause and effect. The Varki Lab at UC San Diego School of Medicine has been working out the rest of the puzzle for more than two decades.

Dr. Nissi Varki, professor of pathology at UC San Diego School of Medicine, and co-author Dr. Ajit Varki, distinguished professor of medicine and cellular and molecular medicine, have been working toward understanding why “naturally occurring coronary heart attacks due to atherosclerosis are virtually nonexistent in other mammals, including closely related chimpanzees in captivity which share human-like risk factors, such as high blood lipids, hypertension and physical inactivity.”

Researchers honed in on N-glycolylneuraminic acid, a sialic acid commonly called Neu5Gc found throughout the animal kingdom, but absent in humans. Around 2 to 3 million years ago, after the Homo genus diverted from hominids, the human genome lost the CMAH gene which builds Neu5Gc in other mammals.

Humans instead have an abundance of naturally occurring N-acetylneuraminic acid. When humans ingest Neu5Gc through red meat, it becomes a source of inflammation.

The loss of NeuG5c in humans (retained in other primates) increases atherosclerosis risk by multiple mechanisms, including intrinsic factors such as heightened inflammatory response and hyperglycemia and extrinsic factors such as red meat-derived Neu5Gc-induced xenosialitis. (Kunio Kawanishi)

In previous research, Dr. Nissi Varki postulated the loss of CMAH might have been a tradeoff for resistance against a form of malaria that targeted Neu5Gc in other mammals. Other research suggests losing the CMAH gene may be advantageous to long-distance runners, and that it allowed human brains to continue growing after birth.

In Monday’s study, the researchers used mice to better understand the role the CMAH gene plays in preventing atherosclerosis. Mice were bred without the CMAH gene, to mimic humans, and fed a high-fat soy-based diet. Compared to mice with the CMAH gene that produced their own Neu5Gc, mice lacking CMAH were twice as likely to develop clogged arteries and heart disease.

In addition to having thicker buildup in their arteries, mice missing CMAH also showed an “impaired glucose tolerance independent of the dietary regime.”

“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 Ajit Varki in a statement. “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.”

Together and separately the Varkis have participated in research dating back more than two decades linking red meat to heart disease.

In an email Dr. Ajit Varki stressed the increased risk of heart disease associated with consuming red meat, and that there are exceptions.

“While eating red meat can further increase the risk of heart attacks and certain types of cancers, moderate consumption also offers benefits,” Ajit Varki said. “Red meat provides high-quality nutrition, especially for women of childbearing age who are often deficient in iron and other key nutrients. But later in life, the risks from red meat consumption rises.”

Researchers intend to further analyze the molecular mechanisms at play, particularly where red meat is concerned.

%d bloggers like this: