Cardiovascular Health Effects Innovation Research Program

National Institute Of Environmental Health Sciences

Investigators

Linked publications & trials

Abstract

The CV HEI Program aims to build a capability that currently does not exist in an area of public health that represents the most significant cause of morbidity and mortality in the world. Accordingly, our program fills an important gap in DTT’s portfolio of models, assays, and assessment approaches. It will provide unique insights into environmental contributions to a significant public health burden and broaden DTT’s approach to identifying human-relevant environmental health hazards. Building this pipeline de novo and aligning it to our fundamental understanding of CV pathobiology should strengthen our ability to experientially build confidence in the predictivity of mechanistic bioactivity screens. Building an innovative disease-screening paradigm will substantially enhance our ability to link environmental exposures to important and contemporary diseases. The CV HEI Program intends to engage the full breadth of the DTT mission and goals, as CV disease is clearly a contemporary public health challenge. The program’s path toward capability development will enable evidence-based approaches beginning with in silico QSAR modeling and medium- to high-throughput bioactivity screening and continuing through complex in vitro confirmatory assays and holistic in vivo assessments in animal models enhanced for evaluation of fundamental physiologic measures. Early predictions informed by in silico models and in vitro bioactivity will be qualified in progressively complex assay systems allowing us to build confidence in early pipeline steps, assess model applicability domains, and identify capability development needs. The assay systems used will be aligned to known human CV failure modes and reflect human biology as much as the complexity of the system permits with a goal of optimizing the translational relevance of the outcomes. We will define a novel paradigm for environmental hazard assessment working collaboratively with government, academic, and industry colleagues. Postdoctoral trainees will contribute to key projects. The CV HEI Program will define and test a full pipeline of capabilities, and the outcomes of our efforts will be communicated in the varied channels available to us, including usual scientific communications (abstracts, presentations, peer-reviewed manuscripts), National Institute of Environmental Health Sciences media platforms and, when appropriate, NTP-branded publications. CV HEI accomplishments • Program scientists developed an interactive systematic evidence map utilizing artificial intelligence approaches to identify, categorize, and integrate data from human, animal, and in vitro studies exploring the effects of environmental exposures on cardiotoxicity to support prioritization of future cardiotoxicity studies. This research was presented earlier in 2024 (Society of Toxicology) and manuscripts are being developed. • Program scientists developed an interactive systematic evidence map utilizing artificial intelligence approaches to identify and characterize data from human and animal studies evaluating biomarkers for hypertensive disorders of pregnancy (HDP). This map will support research that aims to understand how environmental factors may contribute to HDP and to support the identification of biomarkers for early prediction of HDP. This evidence map will be presented at the American Heart Association Hypertension Scientific Sessions 2025 in September. • In collaboration with NCATS, the program is testing chemicals with potential vascular toxicity in HUVEC endothelial cells and in coculture and flow model and is working on the manuscripts. • To support the program, DTT established a contract with Duke University to test several environmental chemicals in their human skeletal muscle myobundles and tissue-engineered blood vessel models in order to evaluate potentially cardiotoxic chemical activity. This work was presented at the Biomedical Engineering Society and the American Society for Cellular and Computational Toxicology in October 2024.