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Updated: Jun 4, 2026
Dynamic Assessments of Coronary Flow Reserve after Myocardial Ischemia Reperfusion in Mice
Published on: August 25, 2023
Genome-wide association study of coronary flow reserve assessed by cardiac perfusion PET suggests a role for NF-κB
Rasika Venkatesh1, Tess Cherlin2, Nicole Wayne3
1Department of Genetics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Insights
Coronary microvascular disease (CMVD) impacts ischemic heart disease (IHD). This study used cardiac PET coronary flow reserve (CFR) to identify genetic links to CMVD, revealing a potential role for the NF-κB pathway.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Coronary microvascular disease (CMVD) is a significant contributor to ischemic heart disease (IHD), necessitating deeper mechanistic understanding and novel therapeutic strategies.
- Quantitative assessment of coronary flow reserve (CFR) using perfusion cardiac positron emission tomography (PET) serves as a key indicator of coronary microvascular function.
Purpose of the Study:
- To investigate genetic associations with CMVD using CFR as a quantitative measure.
- To explore novel genetic loci and pathways implicated in CMVD through genome-wide association studies (GWAS).
Main Methods:
- Gene association study of previously reported IHD loci with cardiac PET-derived CFR.
- Exploratory genome-wide association study (GWAS) for CFR.
- Pathway and proteomic analyses to elucidate biological mechanisms.
Main Results:
- Significant associations were found between known IHD loci and CFR in African (45 loci) and European (18 loci) populations.
- GWAS identified novel loci associated with CFR.
- Multi-omic analyses revealed a significant association between CFR-associated loci and the NF-κB pathway, supported by proteomic data.
Conclusions:
- Genetic factors play a role in coronary microvascular function as measured by CFR.
- The NF-κB pathway is implicated in the pathophysiology of CMVD.
- These findings offer potential targets for CMVD therapies.
Abstract:
Coronary microvascular disease (CMVD) contributes to the large burden of ischemic heart disease (IHD), and there is a need for mechanistic insight and targeted therapies. Perfusion cardiac PET allows for the quantitative assessment of coronary flow reserve (CFR), which reflects coronary microvascular function. Here we use cardiac PET CFR as a measure of CMVD to perform first a gene association study with previously reported IHD loci and, second, an exploratory genome-wide association study. Of 241 known IHD loci, we identify 45 and 18 loci that are associated with CFR in populations genetically similar to African and European populations, respectively. We then perform a genome-wide association study followed by downstream and pathway analyses and identified an association between loci associated with CFR and the NF-κB pathway. We support these associations with targeted proteomic data. Our multi-omic analyses identified potential CMVD loci and suggest a role for the NF-κB pathway in CMVD.
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