Papers of the Month
By Nancy Lamontagne
Air pollution’s effect on the heart
Findings from a decade-long study showed that long-term exposure to air pollution speeds up calcification in arteries that supply blood to the heart. The new findings revealed the biological processes underlying the link between air pollution exposure and increased risk of heart disease.
Using data from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), researchers used home addresses of more than 6,795 people from six U.S. states to assess exposure to air pollutants, including particulate matter smaller than 2.5 microns (PM2.5), nitrogen oxides, and black carbon. Over a period of ten years, CT scans were used to repeatedly measure calcium deposits in the coronary arteries of each participant.
Analysis of the MESA Air data showed that air pollution sped up calcification of the arteries in a way that was consistent with acceleration of atherosclerosis, a condition associated with heart disease. Study participants showed a 20 percent acceleration in the rate of calcium deposits for every 5 micrograms per cubic meter increase in PM2.5, or 35 parts per billion increase in concentration of nitrogen oxides. From 2000 to 2010, study participants experienced an average PM2.5 exposure of 14.2 micrograms per cubic meter, with a range of 9.2 to 22.6. For comparison, today’s U.S. National Ambient Air Quality Standards allow an annual average PM2.5 concentration of 12 micrograms per meter.
Citation: Kaufman JD, Adar SD, Barr RG, Budoff M, Burke GL, Curl CL, Daviglus ML, Roux AV, Gassett AJ, Jacobs DR Jr, Kronmal R, Larson TV, Navas-Acien A, Olives C, Sampson PD, Sheppard L, Siscovick DS, Stein JH, Szpiro AA, Watson KE. 2016. Association between air pollution and coronary artery calcification within six metropolitan areas in the USA (the Multi-Ethnic Study of Atherosclerosis and Air Pollution): a longitudinal cohort study. Lancet; doi:10.1016/S0140-6736(16)00378-0 [Online 24 May 2016].
Comparative Toxicogenomics Database expands into new applications
An NIEHS grantee and colleagues combined gene data from the Gene Ontology (GO) database with information on gene-disease interactions from the Comparative Toxicogenomics Database (CTD) to uncover potential biological similarities between seemingly unrelated diseases. Identifying commonalities among disparate diseases can reveal the biological underpinnings of diseases, pointing toward new therapeutics and diseases that might benefit from existing pharmaceuticals.
CTD is a public database that contains manually curated and coded data from scientific research papers that describe chemical-gene, chemical-disease, and gene-disease interactions. By combining CTD information on genes known to be associated with diseases and GO’s gene data, researchers were able to identify inferred relationships. For example, if gene A is tied to biological process B in GO, and gene A is independently linked with disease C in CTD, then the integrated datasets would show an inferred relationship between biological process B and disease C via gene A.
The researchers produced a resource linking over 15,000 GO annotations to 4,200 human diseases, giving them the ability to detect similarities in biological activities and processes. Using this resource, they discovered and ranked 39 drugs that may be potential therapies for treating chronic B-cell leukemia.
Citation: Davis AP, Wiegers TC, King BL, Wiegers J, Grondin CJ, Sciaky D, Johnson RJ, Mattingly CJ. 2016. Generating gene ontology-disease inferences to explore mechanisms of human disease at the Comparative Toxicogenomics Database. PLoS One 11(5):e0155530.
Pavement sealcoat products may be more toxic than suspected
A study supported in part by NIEHS showed that certain pavement sealcoats used on asphalt driveways and parking lots are significantly more toxic and mutagenic than previously suspected.
The researchers determined the concentrations of 23 polycyclic aromatic hydrocarbons (PAHs) that are classified as unsubstituted PAHs, as well as 56 PAH derivatives and 11 high molecular weight PAHs in coal tar-based and asphalt-based sealcoat products. The high molecular weight PAHs had not been included in previous studies of sealcoat products.
Including the high molecular weight PAH compounds increased the calculated benzo[a]pyrene carcinogenic equivalent by 4.1 to 38.7 percent, suggesting a greater potential risk to human health from coal tar-sealed surfaces than had been previously determined. The asphalt-based sealcoats, which are more commonly used in the western U.S., were toxic, but showed far less toxicity than coal tar sealcoats, which use byproducts of the coal coking process and are more commonly found in the Midwest and East. Further analysis indicated that the asphalt-based products were not mutagenic, but the coal tar-based ones were.
The study results were consistent with previous findings from the U.S. Geological Survey. However, in the new study, the researchers studied a greater number of PAH compounds and found even higher levels of toxicity in sealcoats based on coal tar than had previously been suspected.
Citation: Titaley IA, Chlebowski A, Truong L, Tanguay RL, Massey Simonich SL. Identification and toxicological evaluation of unsubstituted PAHs and novel PAH derivatives in pavement sealcoat products. Environ Sci Technol Lett 3(6):234-242.
New fluorescent sensor provides insights into intracellular heme
An NIEHS grantee and colleagues have developed new fluorescent sensors and used them to track intracellular activity of the iron-containing compound known as heme. The research provides new insights into how cells make heme available in very low concentrations.
Although it can be toxic in larger amounts, miniscule amounts of heme work as an essential cofactor and signaling molecule. Many scientists viewed heme as a static compound that stays bound to the proteins with which it works.
The researchers used their new sensors to follow heme movement in yeast cells and observed, for the first time, that cells contain a variable pool of heme. The researchers also identified some of the biomolecules that help keep most of the pooled heme bound to proteins, while leaving a limited amount free for biochemical reactions. For example, they found that the signaling molecule nitric oxide can rapidly mobilize heme when it is needed for cellular processes such as regulating gene expression.
The new heme sensors can be used in multiple organisms to reveal fundamental aspects of heme dynamics.
Citation: Hanna DA, Harvey RM, Martinez-Guzman O, Yuan X, Chandrasekharan B, Raju G, Outten FW, Hamza I, Reddi AR. 2016. Heme dynamics and trafficking factors revealed by genetically encoded fluorescent heme sensors. Proc Natl Acad Sci U S A; doi:10.1073/pnas.1523802113 [Online 31 May 2016].