Heart attacks in humans are the price of evolution

The loss of a single gene up to three million years ago may explain why humans are at a greater risk of heart disease.

A decade ago scientists discovered homo sapiens are virtually the only animals to suffer heart attacks as a result of plaque accumulating in the arteries.

Our ancestors are thought to have passed down a mutation in the gene CMAH, which has left us unable to produce the sugar molecule Neu5Gc.

When scientists ‘knocked out’ CMAH in mice, the rodents’ arteries started to ‘fur up’. 

The research was carried out by the University of California, San Diego, and led by Dr Ajit Varki, distinguished professor of medicine, and cellular and molecular medicine.

One in four deaths in the US and UK occur due to cardiovascular diseases like heart attacks or strokes, statistics show. 

Atherosclerosis is a leading cause of these disorders. It is defined as the build of plaque in the arteries, which restricts blood flow to the major organs. 

Obesity, smoking and inactivity all raise the risk of atherosclerosis.

However, around 15 per cent of first-time heart disease cases that come on due to atherosclerosis have no obvious cause.

The San Diego scientists were the first to note humans are the only animals to suffer atherosclerosis-related heart attacks.

‘That’s always been a puzzle,’ Professor Varki said. ‘What’s unusual about humans?,’ The Guardian reported.

The cardiovascular events that affect our close ‘relatives’ chimpanzees tend be due to scarring of the heart muscle. The  CMAH gene is found in apes.

To uncover how much Neu5Gc really protects against heart disease, the researchers genetically engineered mice not to produce the sugar molecule.

These rodents went on to have almost twice as severe atherosclerosis as the control animals that still expressed CMAH.

‘The increased risk appears to be driven by multiple factors, including hyperactive white cells and a tendency to diabetes in the human-like mice,’ the authors said.

The scientists believe a genetic mutation that occurred two-to-three millions years ago knocked out CMAH in humans.

This may have been due to a malaria parasite recognising Neu5Gc, they add. Not producing the molecule would therefore have been an evolutionary advantage at the time.

Perhaps surprisingly, exposure to Neu5Gc in our diets could make our heart disease risk worse not better.

Neu5Gc is found in red meat, with exposure triggering an immune response and chronic inflammation, the researchers claim.

In a second part of the experiment, mice that were modified not to express CMAH were fed a Neu5Gc-rich, high-fat diet.

This led to a 2.4 increase in atherosclerosis, which could not be explained by a rise in circulating fats or blood sugar levels.

‘The human evolutionary loss of CMAH likely contributes to a predisposition to atherosclerosis by both intrinsic and extrinsic [dietary] factors,’ the authors wrote.

Exposure to Neu5Gc in mice lacking the CMAH gene has also been linked to inflammation and cancer progression. 

This may explain why a high consumption of red meat is associated with certain tumours, the researchers claimed.