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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月17日

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  • 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 Jr.,
  • Sridhar Rao,
  • Aron M. Geurts,
  • Michael E. Widlansky,
  • Mingyu Liang

摘要

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.