Researchers say the loss of a single gene two to three million years ago in our ancestors may have resulted in a heightened risk of cardiovascular disease in all humans as a species, while also setting up a further risk for red meat-eating humans. The findings are published in PNAS.
Atherosclerosis -- the clogging of arteries with fatty deposits -- is the cause of one-third of deaths worldwide due to cardiovascular disease. There are many known risk factors, including blood cholesterol, physical inactivity, age, hypertension, obesity and smoking, but in roughly 15 percent of first-time cardiovascular disease events (CVD) due to atherosclerosis, none of these factors apply.
A decade ago, researchers noted that naturally occurring coronary heart attacks due to atherosclerosis are virtually non-existent in other mammals, including closely related chimpanzees in captivity which share human-like risk factors, such as high blood lipids, hypertension and physical inactivity. Instead, chimp "heart attacks" were due to an as-yet unexplained scarring of the heart muscle.
In the new study, the researchers report that mice modified to be deficient (like humans) in a sialic acid sugar molecule called N-glycolylneuraminic acid (Neu5Gc) showed a significant increase in atherogenesis compared to control mice, who retain the cytidine monophosphate-N- acetylneuraminic acid (Neu5Ac) hydroxylase (CMAH) gene that produces Neu5Gc.
The researchers believe a mutation that inactivated the CMAH gene occurred a few million years ago in hominin ancestors, an event possibly linked to a malarial parasite that recognized Neu5Gc.
In their findings, the research team said human-like elimination of CMAH and Neu5Gc in mice caused an almost 2-fold increase in severity of atherosclerosis compared to unmodified mice.
"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 the senior author. "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."
But in consuming red meat, humans are also repeatedly exposed to Neu5Gc, which researchers said prompts an immune response and chronic inflammation they call "xenosialitis." In their tests, human-like mice modified to lack the CMAH gene were fed a Neu5Gc-rich, high-fat diet and subsequently suffered a further 2.4-fold increase in atherosclerosis, which could not be explained by changes in blood fats or sugars.
"The human evolutionary loss of CMAH likely contributes to a predisposition to atherosclerosis by both intrinsic and extrinsic (dietary) factors," wrote the authors, "and future studies could consider using this more human-like model."
In previous work, the Varkis and colleagues have shown that dietary Neu5Gc also promotes inflammation and cancer progression in Neu5Gc-deficient mice, suggesting that the non-human sugar molecule, which is abundant in red meat, may at least partially explain the link between high consumption of red meat and certain cancers.
Interestingly, the evolutionary loss of the CMAH gene appears to have produced other significant changes in human physiology, including reduced human fertility and enhanced ability to run long distances.
https://www.pnas.org/content/early/2019/07/18/1902902116
Why only humans are prone to heart attacks
- 1,980 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
'Jumping genes' drive many cancers
Read more
Gene duplications could be fixed with CRISPR/CAS9 and MMEJ repair m…
Read more
Normal mutations in human livers can promote tissue regeneration
Read more
Poverty leaves a mark on our genes
Read more
ALS progression at the genetic and cellular level
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar