Nav: Home

Bioengineers explore cardiac tissue remodeling after aortic valve replacement procedures

September 11, 2019

University of Colorado Boulder engineers and faculty from the Consortium for Fibrosis Research & Translation (CFReT) at the University of Colorado Anschutz Medical Campus have teamed up to develop biomaterial-based "mimics" of heart tissues to measure patients' responses to an aortic valve replacement procedure, offering new insight into the ways that cardiac tissue re-shapes itself post-surgery.

Aortic valve stenosis (AVS), a progressive disease characterized by heart valve tissue stiffening and obstructed blood flow from the heart, is known as a "silent killer," affecting 12.4 percent of the population over 75 years old with a mortality range of 2-5 years if left untreated. Transcatheter aortic valve replacement (TAVR) procedures, which place an artificial valve at the site of the blockage, have been widely and successfully adopted as a remedy in recent decades.

Details of the broader biological reaction to the valve replacement have remained largely unknown, but nevertheless hold significant ramifications for quantifying the quality of recovery, the risk of complications and the assessment of overall patient outcomes.

During AVS disease progression, tissue-specific cells known as fibroblasts transition into myofibroblasts, which promote tissue stiffening. The researchers were interested in understanding how and why, post TAVR, myofibroblasts revert to the more benign fibroblasts.

"Previous studies have shown significant remodeling of cardiac tissues post-intervention," said Dr. Brian Aguado, lead author of the study and a post-doctoral researcher in CU Boulder's Department of Chemical and Biological Engineering. "Our hypothesis was that perhaps there are biochemical cues in a patient's blood that may revert myofibroblasts back to fibroblasts."

Modeling such a transformation in the lab is one thing, Aguado said, but the key to the new study was obtaining blood samples from real AVS patients and then using biomaterials to replicate the microenvironment of the heart.

"The heart is not made of plastic like a petri dish is," he said. "We needed to engineer materials that could reflect the various stiffnesses of both healthy and diseased valve and cardiac tissue."

The researchers collected blood serum samples from AVS patients both pre- and post-TAVR procedure and then treated cardiac cells cultured in a customized hydrogel environment, maintaining a near-facsimile of the in vivo cardiac conditions before and after TAVR.

The researchers were able to quantify protein expression in patient sera, identifying key proteins associated with myofibroblast deactivation as the aortic and cardiac tissue re-shapes and rebuilds itself after TAVR.

"Our lab is focused on engineering hydrogels as mimics of the extracellular tissue microenvironment," said Dr. Kristi Anseth, Distinguished Professor of Chemical and Biological Engineering and director of the Precision Biomaterials IRT. "The hydrogel system developed for these studies enable us to evaluate how patient-specific biochemical cues, found in human sera, can impact cellular phenotypes. Our patient-specific observations would not have been possible using conventional tissue culture plastic materials."

"Cardiac fibrosis due to excess deposition of extracellular matrix proteins is a massive problem," said Timothy McKinsey, professor of medicine and director of the CFReT, one of the programs supported through the University of Colorado School of Medicine's Transformational Research Funding initiative. "Among other things, fibrosis causes the heart to become stiff, impairing its ability to relax. We are excited about the potential of translating our current findings to develop innovative therapies for fibrotic diseases of the heart and vasculature."

The research may also yield future insight into the observed differences in recovery between men and women. Previous clinical studies have suggested that men seem to undergo more cardiac tissue remodeling post-TAVR, and the new data found that male cardiac cells do indeed see more pronounced myofibroblast reversal relative to female cells, though further research is needed to understand sex-specific differences in various clinical contexts.

"We were a bit surprised by the breadth of these findings," Aguado said. "We didn't think that a valve implant could have such a profound impact on the body systemwide. The connections between our engineered models and clinical data give strength to that conclusion."

Overall, Aguado said, the results show that TAVR procedures do indeed trigger a beneficial protein response and that biomaterial models together with clinical samples can provide a useful bridge toward identifying future therapeutic opportunities.

"We are getting better at engineering disease models, but we're reaching a crossroads where models can only do so much," he said. "The future will rely on using patient samples in conjunction with these models to better understand disease progression in a patient. In collaboration with physicians, we can see how our advances in the lab can be translated into identifying more effective treatments for patients."
-end-
The new study was published today in the journal Science Translational Medicine. Additional co-authors of the new study include Joseph Grim, Cierra Walker, Tova Ceccato, Anne Cox and Leslie Leinwand of CU Boulder; Katherine Schuetze and Carmen Sucharov of the University of Colorado Anschutz Medical Campus; Aik-Choon Tan of the Colorado School of Public Health; and Matthew Taylor of the University of Colorado Health Science Center. The National Institutes of Health (NIH), the National Science Foundation (NSF), the American Heart Association, the U.S. Department of Education and the Burroughs Wellcome Fund provided funding for the research.

University of Colorado at Boulder

Related Science Articles:

75 science societies urge the education department to base Title IX sexual harassment regulations on evidence and science
The American Educational Research Association (AERA) and the American Association for the Advancement of Science (AAAS) today led 75 scientific societies in submitting comments on the US Department of Education's proposed changes to Title IX regulations.
Science/Science Careers' survey ranks top biotech, biopharma, and pharma employers
The Science and Science Careers' 2018 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Science in the palm of your hand: How citizen science transforms passive learners
Citizen science projects can engage even children who previously were not interested in science.
Applied science may yield more translational research publications than basic science
While translational research can happen at any stage of the research process, a recent investigation of behavioral and social science research awards granted by the NIH between 2008 and 2014 revealed that applied science yielded a higher volume of translational research publications than basic science, according to a study published May 9, 2018 in the open-access journal PLOS ONE by Xueying Han from the Science and Technology Policy Institute, USA, and colleagues.
Prominent academics, including Salk's Thomas Albright, call for more science in forensic science
Six scientists who recently served on the National Commission on Forensic Science are calling on the scientific community at large to advocate for increased research and financial support of forensic science as well as the introduction of empirical testing requirements to ensure the validity of outcomes.
World Science Forum 2017 Jordan issues Science for Peace Declaration
On behalf of the coordinating organizations responsible for delivering the World Science Forum Jordan, the concluding Science for Peace Declaration issued at the Dead Sea represents a global call for action to science and society to build a future that promises greater equality, security and opportunity for all, and in which science plays an increasingly prominent role as an enabler of fair and sustainable development.
PETA science group promotes animal-free science at society of toxicology conference
The PETA International Science Consortium Ltd. is presenting two posters on animal-free methods for testing inhalation toxicity at the 56th annual Society of Toxicology (SOT) meeting March 12 to 16, 2017, in Baltimore, Maryland.
Citizen Science in the Digital Age: Rhetoric, Science and Public Engagement
James Wynn's timely investigation highlights scientific studies grounded in publicly gathered data and probes the rhetoric these studies employ.
Science/Science Careers' survey ranks top biotech, pharma, and biopharma employers
The Science and Science Careers' 2016 annual Top Employers Survey polled employees in the biotechnology, biopharmaceutical, pharmaceutical, and related industries to determine the 20 best employers in these industries as well as their driving characteristics.
Three natural science professors win TJ Park Science Fellowship
Professor Jung-Min Kee (Department of Chemistry, UNIST), Professor Kyudong Choi (Department of Mathematical Sciences, UNIST), and Professor Kwanpyo Kim (Department of Physics, UNIST) are the recipients of the Cheong-Am (TJ Park) Science Fellowship of the year 2016.
More Science News and Science Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.