Exposure to diesel particles in utero shows association with adult heart failure in mice

A newly published study suggests that exposure to diesel exhaust in utero promotes heart failure later in life. The study, In utero exposure to diesel exhaust particulates is associated with an altered cardiac transcriptional response to transverse aortic constriction and altered DNA methylation, was published in the August 2017 issue of The Journal of the Federation of American Societies for Experimental Biology (FASEB).

Dr. Michael Chin
EDGE Center member Michael T. Chin is the principal investigator. His team used 4 groups of mice. The first group was exposed during gestation to filtered air, then underwent sham surgery as adults. The second group was exposed during gestation to diesel exhaust particulates, then underwent sham surgery as adults. The third group was exposed during gestation to filtered air, then underwent transverse aortic constriction (TAC) surgery as adults, and the final group was exposed during gestation to diesel exhaust particulates, then underwent TAC surgery as adults. TAC surgery is an experimental model used in mice to cause enlargement of the left ventricle of the heart; it leads to heart failure. 

Following the exposures, the expression of heart genes in the four groups was compared. The scientists identified three candidates genes (Mir133a-2, Ptprf, and Pamr1) that were expressed differently in the group of mice exposed to both diesel exhaust and TAC surgery. The target genes identified in this study are the first genes identified as likely playing an role in adult heart failure.

Further examination found that in those mice exposed to both diesel exhaust and TAC surgery, DNA methylation was altered in the promoter region of the Mir133a-2 candidate gene. DNA methylation, also known as epigenetics, consists of chemical groups that attach to the DNA molecule and work as on/off switches to regulate gene expression. 

Mir133a-2 has been identified as a biomarker for patient outcomes after heart valve replacement in humans and is presently being studied as a potential treatment to improve patient outcome after a heart attack. Finding out whether Mir133a-2 can protect against heart failure from exposure to diesel exhaust will help further drug development for patients with heart failure associated with air pollution.

Chin suggests that these findings can inform public policy: "Our study adds to the large body of evidence that air pollution exposure has significant harmful effect on the cardiovascular system, and extends these findings to show the effects of this exposure on the developing heart -- effects that can last for decades. By demonstrating this potential public and global health problem, we hope that our study prompts leaders to develop thoughtful environmental regulatory policies that promote the health and wellbeing of future generations."

Dr. Chin, M.D., Ph.D., is associate professor of medicine at the UW Center for Cardiovascular Biology in the School of Medicine and a member of the UW EDGE Center.

--Marilyn Hair


Addressing Public Health Emergencies through Research: The NIH DR2 Program

Dr. Aubrey Miller from NIEHS presents the
DEOHS Environmental Health Seminar
(photo: Liz Guzy)
The EDGE Center was privileged to host Dr. Aubrey Miller of the National Institute of Environmental Health Sciences (NIEHS) to present the DEOHS Environmental Health Seminar on May 25th. Dr. Miller is Senior Medical Advisor to NIEHS Director Dr. Linda Birnbaum. He leads the NIH Disaster Research Response (DR2) Program and has been extensively involved in the NIH Gulf Oil Spill response, among other national disasters.
When a disaster occurs, the immediate focus is to save lives and protect health. But after these immediate needs are met, questions arise about health effects on communities and rescue workers. There is an opportunity to learn from the disaster and be able to respond better the next time. A great deal of public health work is built on what has been learned from disasters.
But responding to a disaster is all-consuming. The response is not set up to do research. So a goal of DR2 is fill this gap by figuring out how to do well-designed and effectively executed research in and after an emergency. The program aims to assemble tools in a ready-to-go toolkit. Epidemiological tools, bio-specimen kits, and environmental sampling tools are being developed to quickly initiate studies after a disaster.
EDGE Director Terry Kavanagh 
and NIEHS's Aubrey Miller
(photo: Marilyn Hair) 
Dr. Miller said that one of the challenges in a disaster is coordination. No single agency or community has all the tools and information that are needed to respond to a disaster. A multitude of public and private agencies must coordinate efforts.

Also, community involvement is essential. Listening to and addressing community concerns and questions builds cooperation and trust, increases the chance that the right questions are being asked, and offers an opportunity to collect on-the-ground information. DR2 emphases community engagement, helping to apply scientific research to help communities. It's a chance to protect communities. 

While on campus, Dr. Miller also met with researchers from the UW Post-Disaster Rapid Response Research Facility (RAPID), a disaster investigation center that provides instrumentation and tools to collect and assess critical post-disaster data with the goal of reducing physical damage and socio-economic losses from future disasters. More about the new RAPID facility at UW can be found here and here. The goal of the meeting between the EDGE and RAPID Centers was to brainstorm ways for future collaboration, leveraging the unique resources of each Center. 
Dr. Miller and Outreach Manager
Marilyn Hair discuss DR2
(photo: Christine Tran)

The EDGE Center hosted an afternoon reception in Dr. Miller's honor, giving Department of Environmental and Occupational Health Sciences (DEOHS) researchers, staff and students the opportunity to meet him and discuss disaster research response.



--Marilyn Hair





Event Highlight: 5th Annual Living Breath of Wǝɫǝbʔaltxʷ Indigenous Foods & Ecological Knowledge Symposium


The 5th Annual Living Breath of Wǝɫǝbʔaltxʷ Symposium was held May 5-6, 2017 at Wǝɫǝbʔaltxʷ or Intellectual House,* on the University of Washington campus. The symposium was bigger and better than ever.

The meeting began with the leaders acknowledging the Duwamish tribe on whose traditional land the UW is located. Next was an extended Elder Blessing with chanting and speaking by Hyamiciate, Della (Rice) Sylvester (Cowichan), a traditional medicine woman.

Attendees graced Wǝɫǝbʔaltxʷ with native costumes: Ceremonial dresses and shawls, cedar hats, jackets embroidered with symbols from Standing Rock, and caribou-skin boots with sealskin soles worn by Inupiaq youth. I was struck by the many ways participants honored the elders who were present, from bringing them beverages and food samples, to inviting them to the front of the buffet line.

Lunches and snacks were traditional local foods, as you might expect at a conference focused on indigenous foods. I greatly enjoyed seed-filled muffins, strawberries, blueberries, sockeye salmon, nettle pesto, wild rice, elk burgers, seal oil, dried huckleberries, moose jerky, nettle bread and evergreen tree-tip tea. Participants were reminded not to decide you don't like something the first time you taste it. You have to try a new food 6 times to decide whether you like it. 

Speakers came from near and far away: Coast Salish, Alaska and Inupiaq tribes, as well as tribes from eastern Washington, the US southwest, Canada, and Mexico. Presentation topics included soil, corn, seeds, climate resilience, youth leadership, indigenous lands, traditional languages, native curriculum,  traditional foods and beverages, and food sovereignty projects.

The event honored and highlighted Native Youth. The keynote speaker was 16-year old Kalilah Rampanen from Vancouver Island (Nuu-chah-nulth, Woodland Cree and Finnish), a young activist who told her story through words and song. Her presentation on Saturday morning was followed by 13-year old Tim Masso (Tla-o-quiaht/Nu-chah-nulth) who told his story of learning and teaching the Nu-chah-nulth language. He wanted to learn his native language and pressed his school to teach Nu-chah-nulth. At first he was told to take French. When eventually a native language teacher was hired, students were taught just colors and numbers. Tim used books to learn Nu-chah-nulth on his own, and volunteered to teach the class himself. He has become the spokesperson for teaching native languages in schools in British Columbia. Tim concluded his presentation by teaching the audience some Nu-chah-nulth vocabulary: Choo (spelled phonetically) means I'm done. Che KO means Thank you.

Another inspiring presentation was titled, Building Food Sovereignty, Climate Resilience, and Youth Leadership in the Northwest Alaskan Arctic. Four youth from the Inupiaq community of Kivalina, Alaska who worked as interns in the Kivalina Food Sovereign Project presented a vivid story of life and changes in this subsistence fishing-and-hunting community. Kivalina, with 90 households, is located on a barrier island north of the Arctic Circle. Their traditional foods include beluga whale, bearded seal, caribou, moose, and deer. The island is overcrowded and lacks running water. With climate change the ice is melting, affecting animal habitat, bringing more severe storms, and raising the sea level. The oil industry has also destroyed habitat, and a neighboring village dumps waste into the river which flows through Kivalina. A project called Re-locate is working to move the village to the mainland to address overcrowding and provide fresh running water. 

Our partners in Tend, Gather & Grow, Elise Krohn and Valerie Segrest (Muckleshoot), presented their curriculum, Training Track: Empowering Health Champions with a Traditional Beverage Campaign. Their toolkit, coming out May 12th, includes a recipe book called Native Infusion, Rethink Your Drink, and 6 theme posters (Build Strength - nettles; Be Resilient - evergreen fir tips; Food is Our Medicine - huckleberries, and others). Find a description of their May 12th training at the Muckleshoot Elder's Complex on our Native Teach Facebook Page.

Here's the symposium program. It's clear that food sovereignty programs are increasing in number and growing in scope. Congratulations to the eight (mostly native) women academics who volunteered to plan the symposium. 
-- Marilyn Hair

P.S. One of the resource tables displayed traditional Nuu-chah-nulth foods and the community's fish cookbook, Camas. Camas can be ordered from the Nuu-chah-nulth tribe for $12.95. Baked sockeye marinated in maple syrup and soy sauce caught my eye.

*Wǝɫǝbʔaltxʷ is a longhouse-style building that pays homage to the Coast Salish culture and architecture. Wǝɫǝbʔaltxʷ opened in February 2015, the realization of a 40-year dream. The Intellectual House exemplifies the spirit of sharing, cooperation and commitment to indigenous knowledges and local and national indigenous communities.

Tend, Gather & Grow partners with EDGE Center to develop Teaching Toolkit

The Tend, Gather and Grow team

The EDGE Center is pleased to partner with Tend, Gather, and Grow, a team of 13 native and non-native educators from western Washington who are developing a teaching toolkit for children and youth about northwest plants.

Tend, Gather and Grow is project of Garden, Raised, Bounty (GRuB), a non-profit food justice organization in Olympia, WA. Tend, Gather and Grow is dedicated to educating native and non-native young people about wild edible and medicinal plants and the cultural traditions around them. Through developing a teaching toolkit about Northwest plants and providing teacher trainings, the project aims to build food security, promote health, and facilitate connection with the land. Seeing the need to revitalize cultural, nutritional and medicinal knowledge of wild edible plants has emerged as a priority for creating robust tribal food systems.

Early spring violets
The teaching toolkit is directed at young people ages 5-18. Lessons focus on common wild plants and offer supporting material about traditional land management practices, plant identification, harvest protocols, nutrition and cooking, medicine-making, and traditional technologies. Teaching videos will show youth demonstrating their plant knowledge; educator field trip guides will help teachers lead visits to camas prairies, wetlands, forests, saltwater beaches and mountain huckleberry meadows.

The EDGE Center Community Outreach and Ethics Core (COEC) is supporting the development of field trip guides and of a Cultural Ecosystems module. Cultural Ecosystems describes how over thousands of years the land has shaped the culture of Northwest Native People, and, in turn, Native People have shaped the ecologies of the land. The module emphasizes that humans are integral to, not separate from, the natural world.

The lessons will be piloted during 2017 in seven public schools in Thurston, Mason and King Counties, outdoor youth programs, and community classes with Muckleshoot, Nisqually, Squaxin Island, Chehalis and Tulalip tribes. After the pilot, the toolkit will be widely available to educators. The Tend, Gather and Grow team will offer "train the trainer" workshops throughout Washington, Oregon, Southern Alaska and British Columbia to implement the toolkit, as well as provide online access to the materials and updates.

Elise Krohn, educator, author, herbalist and native foods specialist, leads the project team. Rose James, Co-Director of the EDGE Center Community Outreach and Ethics Core (COEC) is a member of the Tend, Gather and Grow team, as are Aleta Poste, Annie Brulé, Brett Ramey, Charlene Rubinstein, Charlie Sittingbull, Elizabeth Campbell, Janna Lafferty, Dr. Joyce LeCompte, Kim Gaffi, Mariana Harvey, and Tracy Rector. Project partners include the Squaxin Island, Muckleshoot, Tulalip, Suquamish, Nisqually, and Puyallup tribes, U.S. Fish and Wildlife Service Connecting People with Nature Program, Washington Dental Health, Hancock Forestry, Pacific Education Institute, and the UW EDGE Center.
-- Marilyn Hair 


"We cannot win this battle to save species and environments without forging an emotional bond between ourselves and nature -- for we will not fight to save what we do not love."  --Shephen J. Gould
                                                                                                           









EDGE Center Investigator Dr. Catherine Karr wins Presidential Early Career Award for Scientists and Engineers

EDGE Center investigator Professor Catherine Karr has received the 2017 Presidential Early Career Award for Scientists and Engineers, the highest honor given by the U.S. government to federally-funded early career research scientists and engineers. 

Dr. Karr is a pediatric environmental medicine specialist and environmental epidemiologist. Her primary appointment is in the Department of Pediatrics. In addition to her role as Director of the Clinical & Translational Services in the EDGE Center, she has an appointment in the Department of Pediatrics, is an adjunct professor of epidemiology, and directs the Northwest Pediatric Environmental Health Specialty Unit (PEHSU), where she sets the direction for outreach and education as well as responding to queries from health care providers, government officials, and families regarding health risks associated with environmental exposures. Dr. Karr cares for patients and teaches residents at the Pediatric Care Center, UW Medical Center-Roosevelt and provides specialty pediatric environmental medicine consultation at Roosevelt and Harborview Medical Center. She is affiliated with the Center for Children's Environmental Health Research and the Pacific Northwest Center for Agricultural Safety and Health (PNASH), both based at UW, and is involved in policy and education through the American Academy of Pediatrics National Council on Environmental Health

Karr uses a community engaged approach to her research focusing on environmental contaminants and pediatric respiratory health — including asthma, the health of farmworker children and global children’s environmental health. Her recent projects include working with Native American and Latino communities in the Yakima Valley to develop low-cost air pollution sensors aimed at reducing wood smoke exposure, conducting an intervention trial among Yakima youth with asthma to evaluate the effectiveness of home air cleaners, and investigating how exposure to environmental factors from conception through early childhood influences the health of children and adolescents. Karr said this about receiving the award: "My success reflects the shared dedication and hard work of community partners and community members who enable community engaged research to be done and be relevant."


Catherine Karr was one of 23 recipients nominated by the U.S. Department of Health and Human Services, and one of just two of 102 total award recipients from the University of Washington.

More than a dozen federal departments or agencies nominate young scientists and engineers from across the country whose “early accomplishments show the greatest promise for assuring America’s preeminence in science and engineering and contributing to the awarding agencies’ missions.” The final awards, first established by President Bill Clinton in 1996, are coordinated by the Office of Science and Technology Policy within the Executive Office of the President. Awardees are selected for their pursuit of innovative research and their commitment to community service as demonstrated through scientific leadership, public education, or community outreach. 

President Barack Obama said in a statement, “I congratulate these outstanding scientists and engineers on their impactful work. These innovators are working to help keep the United States on the cutting edge, showing that federal investments in science lead to advancements that expand our knowledge of the world around us and contribute to our economy.”
--Marilyn Hair

10-year MESA Air study finds air pollution accelerates plaque build-up in arteries to heart

Long-term exposure to air pollution has been linked to an increased risk of heart disease, but the biological process has not been understood. A major, decade-long study of thousands of Americans found that people living in areas with more outdoor pollution —even at lower levels common in the United States — accumulate deposits in the arteries that supply the heart faster than do people living in less polluted areas. The study was published May 24 online in The Lancet.
photoJoel Kaufman
Previous epidemiologic studies have shown associations between particle pollution, referred to as particulate matter, and cardiovascular disease. It has been unclear, however, how exposure to particulate matter leads to disease of the cardiovascular system. The earlier studies had been shorter and had depended for their analysis on existing datasets collected for other purposes.
Now, direct evidence from the Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air), a 10-year epidemiological study of more than 6,000 people from six U.S. states, shows that air pollution — even at levels below regulatory standards — accelerates the progression of atherosclerosis. The condition, also called hardening of the arteries, can cause heart attacks. Researchers repeatedly measured calcium deposits in the heart’s arteries by using CT scans. They also assessed each person’s exposure to pollution based on home address.
“The study provides important new information on how pollution affects the main biological process that leads to heart disease,” said Dr. Joel Kaufman, who directs MESA Air and is the lead author of the published paper. He is a University of Washington professor of environmental and occupational health sciences, and also a UW professor of epidemiology, and of medicine.
Air pollution monitors were deployed in more than 1500 locations within the six different metro areas. In addition to air pollution data from state and local air agencies, these MESA Air monitors collected and measured variable levels of PM2.5, oxides of nitrogen, and black carbon, among other pollutants over two-week periods between 2005-2009.Air pollution monitors were deployed in more than 1500 locations within the six different metro areas. In addition to air pollution data from state and local air agencies, these MESA Air monitors collected and measured variable levels of PM2.5, oxides of nitrogen, and black carbon, among other pollutants over two-week periods between 2005-2009.
“The evidence supports worldwide efforts to reduce exposures to ambient air pollutants,” Kaufman said.
He added, “This was the most in-depth study of air pollution exposures ever applied to a large study group specifically designed to examine influences on cardiovascular health.”
The researchers calculated each participant’s exposure to ambient fine particulate matter that is less than 2.5 microns in diameter and too small to be seen by the naked eye. In addition to PM2.5, they also measured exposure to nitrogen oxide and nitrogen dioxide, and black carbon or soot.
The research team collected thousands of air pollution measurements in the study participants’ communities and at their homes. The research team developed and applied computational models that included local information on land use, roadway and traffic volumes, weather conditions, and local sources of air pollution. These models could generate accurate pollution concentrations at each person’s home. Meanwhile, between the years 2000 and 2012, participants visited study clinics several times to undergo CT scanning to determine the amount of calcium deposits in their heart arteries.
Results were strongest for fine particulate matter and the traffic-related pollutant gases called oxides of nitrogen. The study found that for every 5 µg/m3 higher concentration of PM2.5, or 35 parts per billion higher concentration of oxides of nitrogen — about the difference between more and less polluted areas of a U.S. metropolitan area — individuals had a 4 Agatston units/year faster rate of progression of coronary artery calcium scores. This is about a 20 percent acceleration in the rate of these calcium deposits.
“The effects were seen even in the United States where efforts to reduce exposure have been notably successful compared with many other parts of the world,” Kaufman said. Exposures were low when compared to U.S. ambient air quality standards, which permit an annual average PM2.5concentration of 12 µg/m3. The participants in this MESA-Air study experienced concentrations between 9.2 and 22.6 µg/m3.
The two histograms for PM2.5 and NOx show the range of average, modeled pollution concentrations from 2000-2012 at study participants’ homes in the six metro areas. Exposures were low when compared to U.S. ambient air quality standards, which permit an annual average PM2.5 concentration of 12 µg/m3. The participants in this MESA-Air study experienced concentrations between 9.2 and 22.6 µg/m3.The two histograms for PM2.5 and NOx show the range of average, modeled pollution concentrations from 2000-2012 at study participants’ homes in the six metro areas. Exposures were low when compared to U.S. ambient air quality standards, which permit an annual average PM2.5 concentration of 12 µg/m3. The participants in this MESA-Air study experienced concentrations between 9.2 and 22.6 µg/m3.
In an accompanying editorial in The Lancet, Dr. Bert Brunekreef, a professor at Utrecht University in The Netherlands, and Dr. Barbara Hoffmann, a professor of the University of Düsseldorf in Germany, described the study as “exemplary.” Noting that the results are sobering, they called for decisive action in controlling pollution levels worldwide.
The MESA Air study was funded in 2004 by the U.S. Environmental Protection Agency. The project involved researchers at a number of institutions, and characterized air pollutant exposures experienced by people in the National Heart, Lung, and Blood Institute’s Multi-Ethnic Study of Atherosclerosis (MESA). The participants lived in six major cities across the United States. The clinics were in Baltimore, Chicago, Los Angeles, New York City, St. Paul and Winston-Salem. Of the people in the study, 39 percent were white, 27 percent black, 22 percent Hispanic, and 12 percent Chinese. Other funding for this study came from the National Heart, Lung, and Blood Institute and the National Institute of Environmental Health Sciences.
Authors, in addition to Kaufman, were Sara Adar, R. Graham Barr, Matthew Budoff, Gregory Burke, Cynthia Curl, Martha Daviglus, Ana Diez Roux, Amanda Gassett, David Jacobs, Jr.; Richard Kronmal, Timothy Larson, Ana Navas-Acien, Casey Olives, Paul Sampson, Lianne Sheppard, David Siscovick, James Stein, Adam Szpiro, and Karol Watson. The authors come from institutions that include the University of Washington, Columbia University, University of California, Los Angeles; Wake Forest University, Northwestern University, Johns Hopkins University, University of Michigan, University of Vermont, University of Minnesota, and University of Wisconsin, among others.
-- Elizabeth Sharpe
A map of L.A., California, shows a great deal of variation exists within the city for residential exposures to PM2.5. MESA Air researchers integrated multiple data sources into a computational model to calculate individual residential exposure to pollutants. These sources included: land use, roadway and traffic volumes, weather conditions, local and state agency air pollution measurements, and MESA-Air-deployed monitors.A map of L.A., California, shows a great deal of variation exists within the city for residential exposures to PM2.5. MESA Air researchers integrated multiple data sources into a computational model to calculate individual residential exposure to pollutants. These sources included: land use, roadway and traffic volumes, weather conditions, local and state agency air pollution measurements, and MESA-Air-deployed monitors.