Researchers at UCLA Health investigating the connection between air pollution and cardiovascular disease have uncovered novel blood biomarkers, long-chain dicarboxylate acids (DCAs) and medium- to long-chain acyl-carnitines (ACs), in mouse and human blood samples exposed to air pollution. These biomarkers provide insights on how air pollution damages cell function and increases the risk of heart disease.
BACKGROUND
Previous UCLA Health studies uncovered the link between air pollution and cardiovascular disease, yet the mechanism that triggers this outcome has remained unknown.
Through the discovery of these biomarkers, researchers can now point to the mitochondria as a key player. When mitochondria are damaged, they cannot properly break down fats for energy. Because the body cannot break down these fats normally, DCAs and ACs build up in the blood. The buildup of these products may indicate cellular stress (oxidative stress and lipid damage) in the liver, which can later lead to cardiovascular disease.
METHOD
Researchers identified the biomarkers by analyzing blood samples from mice and humans collected as part of two previous studies (2013 and 2019). In the mouse study, the animals were exposed to diesel exhaust for two weeks. In the human study, 26 healthy, nonsmoking adults from Los Angeles traveled to Beijing during the summers of 2014 and 2015 and were monitored for 10 weeks.
Researchers meticulously identified individual molecules (metabolites) in the mice and human samples and then measured how they increased or decreased when exposed to pollution. They then compared which metabolites were similar between the mice and humans and found circulating levels of long-chain DCAs and medium-to-long-chain ACs were increased in both mice and humans following air pollution exposure. DCAs and ACs have widely been documented among individuals with deficits in fatty acid oxidation, which is associated with mitochondrial dysfunction. These results support the involvement of impaired fatty acid metabolism and mitochondrial dysfunction in the early cardiovascular effects of air pollution.
IMPACT
Air pollution is a global problem, but only a subset of people ultimately develops significant health effects from exposure. There are no indicators of who will be affected until it is relatively late, when cardiovascular, metabolic (dyslipidemia, diabetes), gastrointestinal (fatty liver disease) diseases or cancer develop.
The detection of increased plasma levels of these new biomarkers would enable patients who are healthy to determine when they are being affected at an early stage, before there is more substantial development of cardiovascular, metabolic or gastrointestinal diseases.
AUTHORS
Jesus Araujo, MD, Professor of Medicine at the David Geffen School of Medicine and Professor of Environmental Health Sciences at the Fielding School of Public Health at UCLA, is the lead author of this study.
In addition to Araujo, other authors of the study include: Yan Lin, Xinghua Qiu, Rajat Gupta, Gajalakshmi Ramanathan, Xinchen Lu, Fen Yin, Oliver Fiehn, Junfeng (Jim) Zhang, Joel D. Kaufman, Yifang Zhu, and Michael Rosenfeld.
JOURNAL
The study was published in the September 24th edition of Arteriosclerosis, Thrombosis and Vascular Biology, a publication of the American Heart Association.
FUNDING
This work was supported by the National Institute of Environmental Health Sciences, National Institutes of Health, American Heart Association, National Key Research and Development Program of China, and the National Natural Science Foundation of China.
MEDIA CONTACT
Rocio Cruz, [email protected]
