Multiomics investigation of the female hypertensive human heart

Hypertension affects 1 in 2 adults in the United States and is the leading risk factor for myocardial infarction and chronic kidney disease. While animal models have advanced our understanding of the effects of hypertension on the heart, molecular insight from human cardiovascular tissues is currently lacking. Building upon previous work describing a protocol for the systematic dissection and preservation of whole postmortem human hearts, we performed pilot multiomics analyses of postmortem human hearts from donors with (n = 3) and without (n = 2) hypertension. Using bulk RNA-seq, we identified a higher abundance of transcripts associated with DNA helicase activity, NAD-dependent deacetylase activity, and branched chain amino acid metabolism in hypertension compared to normotension. Using single-nucleus RNA-seq, we identified a loss of contractile vascular smooth muscle cells and greater endothelial cell proliferation associated with hypertension. Lastly, metabolomics revealed an abundance of metabolites upstream of NAD-dependent metabolic steps in fatty acid oxidation and the Krebs cycle, consistent with reductive stress, and a likely funneling of glycolytic intermediates into the pentose phosphate pathway. Together, these methods demonstrate a powerful technique for the investigation of human cardiovascular disease and lend insight into the molecular signature of hypertension in adult cardiac tissue.

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Publication Details

Journal
Physiological Reports
Published
2025-10-01
DOI
https://doi.org/10.14814/phy2.70586
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
0.00

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article

Multiomics investigation of the female hypertensive human heart

Jason Cunha, Jessica L. Fetterman, Adam C. Gower, Robert F. Padera et al.
Physiological Reports
Single-cell and spatial transcriptomics
article

Multiomics investigation of the female hypertensive human heart

Jason Cunha, Jessica L. Fetterman, Adam C. Gower, Robert F. Padera, Jesse D. Moreira, Nathaniel Fisher, Yuriy O. Alekseyev, Deepa M. Gopal, Hardik Shah, Nathan R. Tucker, Aishwarya Anilkumar, Emelia J. Benjamin, Karan K. Smith, Brian Tao, Christopher Williams, Joshua Lepson, Levi Legler, Richard Mitchell, Daniel A. Levy, Seung Hoan Choi, Zachary J. Milstone
article en

Abstract

Hypertension affects 1 in 2 adults in the United States and is the leading risk factor for myocardial infarction and chronic kidney disease. While animal models have advanced our understanding of the effects of hypertension on the heart, molecular insight from human cardiovascular tissues is currently lacking. Building upon previous work describing a protocol for the systematic dissection and preservation of whole postmortem human hearts, we performed pilot multiomics analyses of postmortem human hearts from donors with (n = 3) and without (n = 2) hypertension. Using bulk RNA-seq, we identified a higher abundance of transcripts associated with DNA helicase activity, NAD-dependent deacetylase activity, and branched chain amino acid metabolism in hypertension compared to normotension. Using single-nucleus RNA-seq, we identified a loss of contractile vascular smooth muscle cells and greater endothelial cell proliferation associated with hypertension. Lastly, metabolomics revealed an abundance of metabolites upstream of NAD-dependent metabolic steps in fatty acid oxidation and the Krebs cycle, consistent with reductive stress, and a likely funneling of glycolytic intermediates into the pentose phosphate pathway. Together, these methods demonstrate a powerful technique for the investigation of human cardiovascular disease and lend insight into the molecular signature of hypertension in adult cardiac tissue.

Physiological ReportsVol. 13(19)
Broad Institute (US), Boston University (US), Brigham and Women's Hospital (US), Boston Medical Center (US), Harvard University (US), SUNY Upstate Medical University (US), University of Illinois Chicago (US), National Heart, Lung, and Blood Institute (US), Framingham Heart Study (US)
National Institutes of Health, Clinical and Translational Science Institute, Boston University, National Heart, Lung, and Blood Institute, National Center for Advancing Translational Sciences
Openalex Percentile: Top 76%
Single-cell and spatial transcriptomics
DOIOpen Access PDFOpenAlex
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