Cardiovascular diseases are the number one killer in the world – and it turns out we might have a two million year old ancestor to blame. Researchers at the University of California San Diego (UCSD) have pinpointed a single gene that ancient ancestors lost, which appears to have predisposed us as a species towards higher rates of atherosclerosis than other apes and mammals.
Atherosclerosis is a condition where the arteries become clogged with deposits of fats or cholesterol. This impedes blood flow and can go on to cause blood clots, aneurysms, heart attacks and other issues related to cardiovascular disease. Risk factors come down to the usual suspects, such as obesity, diabetes, poor diet, smoking and physical inactivity.
But strangely enough, about 15 percent of heart attacks caused by atherosclerosis happen without those risk factors at play. Things get weirder when you look at other mammals – atherosclerosis-related heart attacks are almost uniquely human. A 2009 study showed that in our closest relative, chimpanzees, the condition almost never caused heart attacks, even when the animals were physically inactive and had other risk factors.
So the researchers on the new study – the same team from the 2009 chimp study – set out to investigate. They found that a human-specific gene mutation seems to be the underlying cause of our vulnerability to cardiovascular disease, brought on by atherosclerosis. This same gene may even be responsible for why red meat increases that health risk.
The gene in question is known as CMAH, and it produces a sialic acid sugar molecule called Neu5Gc. As a result of this gene mutation, humans on the whole are deficient in Neu5Gc, which appears to be the root of why atherosclerosis is so much more dangerous to us.
To test out the idea, the UCSD team engineered mice to knock out the CMAH gene, causing a human-like deficiency in Neu5Gc. Sure enough, atherosclerosis was found to be twice as severe in the edited mice as it was in an unmodified control group.
"The increased risk appears to be driven by multiple factors, including hyperactive white cells and a tendency to diabetes in the human-like mice," says Ajit Varki, co-author of the study. "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."
It might sound like an easy problem to solve then – Neu5Gc supplements should surely help prevent cardiovascular diseases, right? But interestingly, the opposite seems to be true. The team found that when they engineered mice to be Neu5Gc-deficient, and then fed them a diet high in Neu5Gc, atherosclerosis rose another 2.4 times over. It appears to trigger an immune response and cause chronic inflammation.
Since Neu5Gc is abundant in red meat, this could go a long way towards explaining why a carnivorous diet is so bad for our cardiovascular systems.
The researchers believe they managed to trace the problem back deep into our shared history. At some point between two and three million years ago, the CMAH gene was inactivated in a hominin ancestor of ours, which the team suggests could have been linked to a malarial parasite.
Evolution rarely takes without giving something back though, and CMAH has a complicated relationship with our health. While its absence may leave us vulnerable to cardiovascular disease and even reduce fertility, we may also be protected from viruses that target Neu5Gc. It's even been implicated in boosting our ability to run longer distances.
The research was published in the journal PNAS.
Source: UCSD via Medical Xpress