A new study combining a controlled mouse experiment with a small human cohort found similar changes in fat-related metabolites after exposure to polluted air, offering evidence that mitochondrial stress may be one pathway linking air pollution to cardiovascular disease.
By yourNEWS Media Newsroom.
Air pollution may affect more than the lungs and blood vessels, with new research suggesting that polluted air can also alter how the body processes fats and place additional stress on mitochondria, the structures responsible for producing much of a cell’s energy.
The peer-reviewed study compared mice exposed to diesel exhaust with 26 healthy adults who traveled from Los Angeles to Beijing for 10 weeks. Researchers found overlapping changes in several metabolic pathways in both groups, particularly molecules associated with fatty-acid processing and mitochondrial function.
The findings do not prove that air pollution causes mitochondrial dysfunction in humans. The human portion of the study was small, and researchers measured short-term biological changes rather than following participants long enough to determine whether those changes ultimately led to cardiovascular or metabolic disease.
The study nevertheless provides a possible biological explanation for some of the long-established links between air pollution and heart disease.
Researchers from UCLA, Duke University, the University of Washington and other institutions analyzed blood metabolites from both humans and mice, looking for patterns that appeared consistently after exposure to higher pollution levels.
In the animal experiment, genetically modified mice prone to atherosclerosis were exposed either to diesel exhaust or filtered air for two weeks.
Researchers had previously found that diesel exhaust exposure in these animals increased blood lipids and disrupted mitochondrial function in the liver.
The new analysis was designed in part to determine whether similar biochemical changes could also be detected in people.
The human portion relied on blood samples collected during an earlier natural experiment involving 26 healthy nonsmoking adults from Los Angeles who spent 10 weeks in Beijing during the summers of 2014 and 2015.
Fine-particle pollution was substantially higher in Beijing.
Average PM2.5 concentrations were approximately 67.6 micrograms per cubic meter there, compared with roughly 14.4 micrograms per cubic meter in Los Angeles, according to the study.
Earlier research involving the same participants found that their exposure to several combustion-related polycyclic aromatic hydrocarbons increased sharply during the Beijing stay and was accompanied by changes in biomarkers associated with oxidative stress and inflammation.
In the latest analysis, researchers used metabolomics and lipidomics to identify molecules that increased or decreased in both species after pollution exposure.
Five major metabolic pathways showed overlapping changes: dicarboxylic acids, acylcarnitines, tryptophan, pyrimidine and lysine metabolism.
Two classes of molecules stood out in particular.
Long-chain dicarboxylic acids and medium- to long-chain acylcarnitines increased in both the mice and the human participants after pollution exposure.
Those compounds can accumulate when cells have difficulty fully breaking down fatty acids for energy.
Mitochondria normally transport fatty acids into their interior, break them down through beta-oxidation and use the resulting molecules to help generate cellular energy.
When that process is impaired, partially metabolized fats can accumulate in forms such as acylcarnitines.
UCLA researchers said the findings therefore point toward mitochondrial stress as a potential link between air pollution and cardiovascular disease.
“When mitochondria are damaged, they cannot properly break down fats for energy,” UCLA Health explained in announcing the findings. Accumulating dicarboxylic acids and acylcarnitines may consequently serve as blood markers of impaired fatty-acid oxidation.
The mouse experiments provided stronger mechanistic evidence than the human portion.
Tests of liver tissue showed impaired mitochondrial energy production after diesel exhaust exposure, reinforcing the connection between the altered blood metabolites and actual changes in cellular energy metabolism.
Researchers could not perform the same invasive liver testing in the human volunteers.
That means the increased acylcarnitines and related metabolites found in people are consistent with mitochondrial dysfunction but do not independently prove that their mitochondria were damaged.
The distinction is one of the study’s central limitations.
Researchers described the overlapping metabolic profile as a “signature” of mitochondrial dysfunction and suggested that the compounds could eventually be investigated as biomarkers for early cardiovascular effects from pollution exposure.
The study also identified evidence of oxidative stress.
Oxidative stress occurs when production of reactive molecules exceeds the body’s ability to neutralize them, potentially damaging lipids, proteins, DNA and cellular structures.
Mitochondria are particularly relevant because they are both major producers of cellular energy and sensitive targets of oxidative injury.
The participants’ earlier Beijing study found elevated metabolites linked to lipid oxidation after exposure to substantially higher levels of combustion-related pollutants.
Previous research has also documented other associations between particulate pollution and mitochondrial changes. Studies of highly exposed populations in Beijing, for example, have reported changes in mitochondrial DNA markers associated with particulate exposure, although those findings similarly do not by themselves establish long-term disease.
The new findings add mitochondrial metabolism to a cardiovascular pathway that already includes inflammation, oxidative stress and vascular dysfunction.
Air pollution, particularly fine particulate matter known as PM2.5, has been associated in large epidemiological studies with increased risks of heart attack, stroke and cardiovascular death.
Scientists have proposed several mechanisms.
Very small particles and chemicals carried on them can trigger inflammatory responses in the lungs, alter autonomic nervous system activity, affect blood clotting and impair blood-vessel function.
The new research suggests disrupted cellular fat metabolism may operate alongside those better-established mechanisms.
The authors emphasized that the 26-person human study is far too small to establish clinical risk on its own.
Participants were also young and healthy, with an average age of about 24 in the original cohort, so the results may not apply directly to older adults or people who already have cardiovascular or metabolic disease.
The exposure change was also unusual.
Rather than comparing people permanently living in different cities, researchers followed the same Los Angeles residents as they traveled temporarily to a substantially more polluted environment.
That design reduced some differences that normally complicate comparisons between populations, since each participant effectively served as his or her own reference.
But it also means the study examined relatively short-term changes over 10 weeks rather than decades of exposure.
Researchers did not determine whether the metabolic changes persisted after participants returned to Los Angeles or whether they translated into clinical disease later in life.
The findings therefore offer a possible mechanism rather than evidence that any particular individual exposed to pollution will develop mitochondrial disease.
They also should not be interpreted as evidence that air pollution is the only environmental factor capable of disturbing cellular metabolism.
Researchers have separately investigated endocrine-disrupting chemicals, heavy metals and other environmental exposures for potential effects on metabolic, neurological and cardiovascular health.
Those are distinct research areas and were not evaluated in the new air-pollution study.
For people seeking to reduce their exposure, federal health guidance emphasizes limiting the amount of polluted air actually inhaled rather than attempting to counteract it through supplements or other unproven treatments.
The Environmental Protection Agency advises people to check the Air Quality Index when particulate pollution or wildfire smoke is elevated and modify strenuous outdoor activity accordingly.
Exercising increases breathing rate and therefore increases the amount of pollution entering the lungs.
When particle levels are high, EPA guidance recommends reducing exercise intensity, shortening time outdoors or waiting until air quality improves.
Moving strenuous workouts indoors can reduce exposure if indoor air is cleaner.
For homes affected by persistent outdoor pollution or wildfire smoke, the EPA recommends high-efficiency filtration, including appropriately sized portable air cleaners or efficient HVAC filters.
Those measures can lower indoor concentrations of fine particulate matter, although their effectiveness depends on the size of the room, the air cleaner’s capacity, filter efficiency and how frequently the equipment operates.
The new research does not establish that HEPA filtration prevents mitochondrial dysfunction or cardiovascular disease. Its benefit is more straightforward: reducing the amount of fine particulate pollution a person inhales.
Researchers say the next step is to determine whether the newly identified metabolites can reliably predict cardiovascular effects in larger and more diverse populations.
If confirmed, acylcarnitines and dicarboxylic acids could potentially become measurable early indicators of biological stress from pollution before overt cardiovascular disease develops.
For now, the strongest conclusion is narrower.
Mice exposed to diesel exhaust developed impaired mitochondrial function and altered fat metabolism, while humans temporarily exposed to substantially higher ambient pollution showed several of the same metabolic signals in their blood.
That cross-species overlap strengthens the case for investigating mitochondria as another pathway through which polluted air may affect cardiovascular health, but much larger human studies will be needed before researchers can establish how directly those biochemical changes translate into disease.
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