Chromatin interaction maps of human arterioles reveal mechanisms for the genetic regulation of blood pressure

Yong Liu, Rajan Pandey, Qiongzi Qiu, Pengyuan Liu, Hong Xue, Jingli Wang, Bhavika Therani, Rong Ying, Kristie Usa, Michael Grzybowski, Chun Yang, Manoj K. Mishra, Andrew S. Greene, Allen W. Cowley, Sridhar Rao, Aron M. Geurts, Michael E. Widlansky and Mingyu Liang ()
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Yong Liu: University of Arizona College of Medicine—Tucson
Rajan Pandey: University of Arizona College of Medicine—Tucson
Qiongzi Qiu: University of Arizona College of Medicine—Tucson
Pengyuan Liu: University of Arizona College of Medicine—Tucson
Hong Xue: Medical College of Wisconsin
Jingli Wang: Medical College of Wisconsin
Bhavika Therani: University of Arizona College of Medicine—Tucson
Rong Ying: Medical College of Wisconsin
Kristie Usa: Medical College of Wisconsin
Michael Grzybowski: Medical College of Wisconsin
Chun Yang: Medical College of Wisconsin
Manoj K. Mishra: University of Arizona College of Medicine—Tucson
Andrew S. Greene: The Jackson Laboratory
Allen W. Cowley: Medical College of Wisconsin
Sridhar Rao: Versiti Blood Research Institute
Aron M. Geurts: Medical College of Wisconsin
Michael E. Widlansky: Medical College of Wisconsin
Mingyu Liang: University of Arizona College of Medicine—Tucson

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract Arterioles are small blood vessels located just upstream of capillaries in nearly all tissues. Despite the broad and essential role of arterioles in physiology and disease, current knowledge of the functional genomics of arterioles is largely absent. Here, we report extensive maps of chromatin interactions, single-cell expression, and other molecular features in human arterioles and uncover mechanisms linking human genetic variants to gene expression in vascular cells and the development of hypertension. Compared to large arteries, arterioles exhibited a higher proportion of pericytes which were enriched for blood pressure (BP)-associated genes. BP-associated single nucleotide polymorphisms (SNPs) were enriched in chromatin interaction regions in arterioles. We linked BP-associated noncoding SNP rs1882961 to gene expression through long-range chromatin contacts and revealed remarkable effects of a 4-bp noncoding genomic segment on hypertension in vivo. We anticipate that our data and findings will advance the study of the numerous diseases involving arterioles.

Date: 2025
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DOI: 10.1038/s41467-025-61656-7

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