Coronary Artery Bypass Grafting (CABG) is a surgery to improve blood supplies to the heart tissue and can effectively treat myocardial ischemia caused by coronary artery diseases. In CABG, a healthy blood vessel will be taken from the patient and be connected to the diseased artery so that the blood could bypass the blocked coronary artery region. Healthy blood vessels used for CABG are mainly arteries from other parts of the patient body, including Internal Thoracic Artery (ITA), Radial Artery (RA) and Right Gastroepiploic Artery (RGA). Among these donor arteries, ITA has the best long-term outcome, whereas RA and RGA are prone to intimal hyperplasia, atherosclerosis and vasospasm.
WANG Xiujie's group at the Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences, in collaboration with SONG Jiangping's group at Fuwai Hospital, Chinese Academy of Medical Sciences, used single-cell RNA sequencing (
scRNA-seq) to elucidate the cell type composition and gene expression profiles of
ITA,RA and RGA.
They found that these three types of donor arteries differed in lipid particle uptake, hemodynamics, vasospasm and fibrosis. Combined with experimental validation in human cells and mice, the following four optimized strategies for CABG were proposed: 1) Inhibition of Macrophage migration Inhibitory Factor (MIF) could reduce intimal hyperplasia of RA; 2) Potassium channel openers could counteract calcium antagonist-unresponsive vasospasm in RGA; 3) Inhibition of CREB5 and GDF10 could reduce extracellular matrix deposition and fibrosis in RA and RGA; 4) PCSK9 inhibitors are recommended for lipid-lowering treatment in ITA.
It is expected to provide guidance for the establishment of clinical CABG surgical strategies and the selection of postoperative drugs.
The results entitled “Strategies for arterial graft optimization at the single-cell level” were published online in Nature Cardiovascular Research on April 25, 2024. SONG Jiangping and WANG Xiujie were the co-corresponding authors, while HU Zhan from Fuwai Hospital, DAI Min from IGDB and CHANG Yuan from Fuwai Hospital, were the co-first authors.
The study was supported by the National Natural Science Fund of China, CAMS Innovation Fund for Medical Sciences, National High Level Hospital Clinical Research Fund, Chinese Academy of Sciences for Young Scientists in Basic Research Project and Beijing Municipal Science & Technology Commission.
Figure. Profiling of the 38,814 single cells isolated from three types of donor arteries
a, Schematic of overall study design. b, UMAP plot of the integrated donor artery datasets, with cells colored according to the major cell types. c, UMAP plots showing the composition and similarities of major cell types in each donor arteries. (Image by IGDB)
Contact:
Dr. WANG Xiujie
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences