Creation of the Framingham Heart Study Cardiovascular Biobank and Atlas
openNHLBI - National Heart Lung and Blood Institute
Abstract
Cardiovascular risk factor burden heavily impacts most cardiovascular disease (CVD) events. A longer
duration of CVD risk factor exposure is associated with elevated risk of CVD and reduced longevity. The
complex phenotypic variation and duration of multimorbidity in individuals results in unique challenges in
understanding the underlying pathobiology of CVD. Currently, our knowledge of human cardiac tissue biology
in CVD is based upon small numbers of chamber biopsies or postmortem sampling in select diseases, and are
largely restricted to White individuals, limiting generalizability. Human cardiovascular tissue multiomics paired
with longitudinal clinical, imaging, and CVD risk factor data are currently unavailable. Consequently, the effect
of CVD risk factors on human cardiovascular tissues is largely unknown. To address these gaps, we propose
to create the Framingham Heart Study (FHS) Cardiovascular Biobank and Atlas. The FHS investigators have
collected clinical, biomarker, and omics data longitudinally across 3 generations and 2 non-European ancestral
cohorts. We propose to create the FHS Cardiovascular Biobank consisting of a systematic and detailed
postmortem cardiac and blood vessel tissue repository from consented FHS participants (n=208, Aim 1A). A
survey of interest and of potential barriers and facilitators for cardiac donation in NHLBI participants with
diverse genetic ancestries (FHS, including Omni 1 & 2, MESA) will be conducted. Community engagement
events in MESA will enable future expansion. A web-based portal, the FHS Cardiovascular Atlas, will be
created to digitally catalog the cardiac biospecimens, provide information regarding biospecimen and data
availability, and transparency on the review process for global research community access via review and
approval through an external biorepository committee (Aim 1B). In Aim 2, single-nucleus RNA-Seq will be
performed in biospecimens from 3 cardiovascular sites (left atrium and ventricle, pulmonary vein) obtained in
Aim 1A. In cross-sectional analyses, we will evaluate the association of the cell type proportions and
transcriptomic signatures with individual CVD risk factors by anatomic site. We will perform RNAscope and
immunofluorescence staining to validate the cell types and transcript/protein levels of differentially expressed
genes in top pathways associated with the CVD risk factors. We hypothesize that premortem CVD risk factors
affect the cell type proportions present and that CVD risk factor-related gene expression patterns will differ by
anatomic site. Use of induced pluripotent stem cell-derived cardiovascular cells, generated from the same
individuals of biobank cardiovascular samples, will allow novel mechanistic inquiries that underlie cardiac
tissue phenotypes in the future. The FHS Cardiovascular Biobank and Atlas will advance our understanding of
the relation of cardiovascular risk factors and disease with cardiovascular structure/phenotype and enable us
to identify new biomarker signatures and mechanisms of CVD in an unprecedented and systematic manner.
Gopal-Fetterman 1
Up to $1.5M
health research