Heart Attacks are Common in Humans: Here’s Why

Loss of a single gene in modern humans during the evolutionary process from our hominin ancestors nearly 3 million years ago might be the reason why humans are predisposed to heart attacks, which are rare in other animals, reveals a recent research at the University of California San Diego School of Medicine.

Heart Attacks Extremely Rare in Other Mammals

• Heart attacks due to coronary artery atherosclerosis are virtually not reported in other mammals, including chimpanzees in captivity which are closely related and share human-like risk factors, such as high blood pressure, high cholesterol levels and physical inactivity.
• Other primates including chimps and great apes have the CMAH gene which is absent in humans
• Chimp "heart attacks" have been found to occur due to scarring of the heart muscle, the cause of which remains unclear

Effect of Loss of CMAH Gene and Rate of Atherosclerosis

• The study team conducted their research comparing test mice genetically modified to resemble humans (knocking off the CMAH gene) with control mice that retained the CMAH gene
• The group of genetically modified mice without the CMAH gene became deficient in Neu5Gc (a sugar molecule) which is encoded by the CMAH gene
• These mice demonstrated a significant increase in the rate of atherogenesis compared to mice that had intact CMAH gene and normal Neu5Gc activity
• Elimination of CMAH gene and Neu5Gc activity in genetically modified mice caused nearly double the severity of atherosclerosis in comparison to unmodified mice
• At the same time, when mice modified to lack the CMAH gene (similar to humans) were fed a diet high in Neu5Gc such as red meat and fats, they showed a further 2.4-fold increase in atherosclerosis, that could not be explained by changes in blood sugar and lipid levels

The authors feel that several other factors may also play a role in increasing heart attack risk in humans, and further investigation is needed.

Prediction of Atherosclerosis Risk Through a Blood Cell Marker
The appearance of sub-clinical atherosclerosis can be predicted by the identification of a molecule CD69 in blood cells, independant of classic cardiovascular diseases.

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Ajit Varki, MD, Distinguished Professor Of Medicine and Cellular And Molecular Medicine at University of California San Diego School of Medicine, and co-author of the study said: "The increased risk (of atherosclerosis) appears to be driven by multiple factors, including hyperactive white cells and a tendency to diabetes in the human-like mice. 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."

How Loss of CMAH Gene Causes Atherosclerosis

As stated earlier, due to loss of the CMAH gene, humans are naturally deficient in Neu5Gc sugar and are prone to accelerated atherosclerosis.

Interestingly, red meat, dairy products and certain fish are rich in this Neu5Gc sugar.  

When humans consume products rich in this sugar, there is an immune response to the sugar, which is recognized as foreign. This immune response produces a generalized state of inflammation in the body, which in turn increases risk of atherosclerosis and heart disease, arthritis and certain cancers.

Other Effects of Loss of CMAH Gene in Humans

Other significant alterations in the human body due to evolutionary loss of CMH gene, including increased exercise capacity and ability to run long distances and a reduced fertility rate.

In summary, loss of CMAH gene and other factors may explain why humans are prone to heart attacks compared to other animals and why some persons with no known identifiable risk factors suffer heart attacks.

References :

1. Human species-specific loss of CMP-N-acetylneuraminic acid hydroxylase enhances atherosclerosis via intrinsic and extrinsic mechanisms - (https://www.pnas.org/content/early/2019/07/18/1902902116)
2. A Single Gene Mutation May Have Helped Humans Become Optimal Long-Distance Runners - (https://health.ucsd.edu/news/releases/Pages/2018-09-11-single-gene-mutation-may-have-helped-humans-become-optimal-long-distance-runners.aspx)

Source: Medindia