In the study,we foud that BTBD7_hsa_circ_000563 were involved in atherosclerotic changes in human being coronary artery segments. And, the expression levels of BTBD7_hsa_circ_000563 were higher in relatively normal coronary artery segments, as compared with in coronary artery segments with severe atherosclerosis. In addition, by means of a proteomics approach, 49 proteins regulated by enhanced BTBD7_hsa_circ_000563 expression were identified in human coronary artery segments. Among these 49 proteins, none of them have been identified as BTBD7_hsa_circ_000563 regulated target protein. Therefore, the results from the present study provides an abundant source for the functional studies of BTBD7_hsa_circ_000563 in coronary artery.
BTBD7_hsa_circ_000563 is located on chromosome 14, and the gene coding starts from position 93,760,203 and ends on position 93,762,503 of chromosome 14 (https://circinteractome.nia.nih.gov/bin/circsearch?circrna=hsa_circ_0000563), and the BTBD7_hsa_circ_000563 was first reported by Memczak et al . Afterwards, significantly different expression of the BTBD7_hsa_circ_000563 was found at human cells (H1hesc, Nhek, and Ag04450) , human different brain regions , and human endothelial progenitor cells  via RNA Sequencing analysis. However, the present study demonstrated that coronary artery segments with severe atherosclerotic stenosis showed extremely low expression of the BTBD7_hsa_circ_000563, as compared with normal coronary artery segments. Furthermore, it was predicted that hsa-miR-155-5p, and hsa-miR-130a-3p are targets of the BTBD7_hsa_circ_000563. The above results of the present study laid an epigenetic foundation for studying the underlying mechanisms of the development of coronary artery atherosclerosis. However, the proteome-wide analysis of BTBD7_hsa_circ_000563-regulated protein in coronary artery has not been reported.
To further explore the foundation and mechanism underlying the association between the BTBD7_hsa_circ_000563 and coronary artery atherosclerosis. The proteome-wide analysis was conducted in the present study. The proteomics analysis identified 49 proteins regulated by BTBD7_hsa_circ_000563 overexpression in human coronary artery segments. And, bioinformatic analyses revealed that a large number of differentially expressed proteins were located in mitochondrion and involved in citrate cycle (TCA cycle) pathway, and the ATP synthase may be the hub of the regulatory networks of BTBD7_hsa_circ_000563 in coronary artery.
As complex dynamic organelles, mitochondria play numerous functions pertaining to cellular metabolism and homoeostasis, the hallmark of mitochondria is cellular energy generation by means of oxidative phosphorylation (OXPHOS) [12–13]. And, the mitochondrial DNA encodes only 13 OXPHOS proteins; the remaining about 1500 proteins from the mitochondrial proteome are transferred to the mitochondria and are encoded in the nuclear genome. In addition, several converging metabolic pathways including the folate metabolism, TCA cycle, and sulphur metabolism consist in whole or partial components of the mitochondria house 。
Coronary artery disease has complex etiology, and mitochondrial dysfunction exerts influence on various celluar aberrations including energy deficit, deregulation of autophagy, metabolic abnormalities, excessive production of reactive species, endoplasmic reticulum stress, and activation of apoptosis. The impairment of the ATP synthesis and respiratory chain have been considered as a key of mitochondrial dysfunction. Therefore, recovering of the mitochondrial function including respiratory activity and ATP-producing capacity have been considered as a primary therapeutic target to improve the prognosis of coronary artery disease . Recently, results from a study suggest that the serum concentration of mitochondrial ATP synthase inhibitory factor 1 is independently negatively associated with all-cause and cardiovascular mortality in subjects with coronary artery disease , and another study suggest ectopic ATP synthase on endothelial cells is considered as a potential and novel therapeutic target for coronary artery disease .