CXCL12 drives natural variation in coronary artery anatomy across diverse populations

IF 45.5 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Pub Date : 2025-03-05 DOI:10.1016/j.cell.2025.02.005

Pamela E. Rios Coronado, Jiayan Zhou, Xiaochen Fan, Daniela Zanetti, Jeffrey A. Naftaly, Pratima Prabala, Azalia M. Martínez Jaimes, Elie N. Farah, Soumya Kundu, Salil S. Deshpande, Ivy Evergreen, Pik Fang Kho, Qixuan Ma, Austin T. Hilliard, Sarah Abramowitz, Saiju Pyarajan, Daniel Dochtermann, Scott M. Damrauer, Kyong-Mi Chang, Themistocles L. Assimes

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引用次数: 0

Abstract

Coronary arteries have a specific branching pattern crucial for oxygenating heart muscle. Among humans, there is natural variation in coronary anatomy with respect to perfusion of the inferior/posterior left heart, which can branch from either the right arterial tree, the left, or both—a phenotype known as coronary dominance. Using angiographic data for >60,000 US veterans of diverse ancestry, we conducted a genome-wide association study of coronary dominance, revealing moderate heritability and identifying ten significant loci. The strongest association occurred near CXCL12 in both European- and African-ancestry cohorts, with downstream analyses implicating effects on CXCL12 expression. We show that CXCL12 is expressed in human fetal hearts at the time dominance is established. Reducing Cxcl12 in mice altered coronary dominance and caused septal arteries to develop away from Cxcl12 expression domains. These findings indicate that CXCL12 patterns human coronary arteries, paving the way for “medical revascularization” through targeting developmental pathways.

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来源期刊

Cell 生物-生化与分子生物学

CiteScore

110.00

自引率

0.80%

发文量

396

审稿时长

2 months

期刊介绍： Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO). The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries. In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.