近日，美国斯坦福大学教授Themistocles L. Assimes及其研究小组发现CXCL12驱动不同人群冠状动脉解剖结构的自然变异。这一研究成果于2025年3月5日发表在国际顶尖学术期刊《细胞》上。
利用6万名不同血统的美国退伍军人的血管造影数据，该研究组进行了冠状动脉显性的全基因组关联研究，揭示了中度遗传性并确定了10个显著位点。在欧洲和非洲血统的队列中，最强的关联发生在CXCL12附近，下游分析暗示对CXCL12表达的影响。该研究团队发现CXCL12在建立优势地位时就在人类胎儿心脏中表达。在小鼠中减少Cxcl12会改变冠状动脉的优势地位，并使中隔动脉远离Cxcl12表达域。这些发现表明，CXCL12可以调控人类冠状动脉，通过靶向发育途径为“医学血运重建”铺平道路。
据介绍，冠状动脉有一种特殊的分支模式，对心肌充氧至关重要。在人类中，关于左下/左后心脏的完善，冠状动脉解剖结构存在自然变异，它可以从右动脉树，左动脉树或两者分支-一种称为冠状动脉优势的表型。
附：英文原文
Title: CXCL12 drives natural variation in coronary artery anatomy across diverse populations
Author: 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, Michael G. Levin, Virginia D. Winn, Anca M. Paca, Mary E. Plomondon, Stephen W. Waldo, Philip S. Tsao, Anshul Kundaje, Neil C. Chi, Shoa L. Clarke, Kristy Red-Horse, Themistocles L. Assimes
Issue&Volume: 2025-03-05
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.
DOI: 10.1016/j.cell.2025.02.005
Source: https://www.cell.com/cell/abstract/S0092-8674(25)00161-8