Atherosclerosis ; genetics ; Chromosomes, Human, Pair 9 ; Humans ; RNA, Long Noncoding

Objective To analyze the research status,hotspots,and frontiers of atherosclerosis genomics from 2010 to 2019.Methods CiteSpace software was used to conduct data statistics and visual analysis on countries,institutions,authors,journals,co-cited papers,and keywords of the related papers published in the Web of Science from 2010 to 2019.Results A total of 1021 papers in English were included,and the annual number of publications generally showed an upward trend.The knowledge base in the research of atherosclerosis mostly focused on the genetic risk sites and biomarkers for coronary artery diseases such as coronary heart disease,myocardial infarction,and dyslipidemia.The related journals mainly involved the fields of molecular biology,biology,genetics,immunology,medicine,pharmacy,and clinical medicine.The latest research in atherosclerosis concentrated on genome-wide association study,DNA methylation,microRNA,messenger RNA and so on.The research frontiers involved long noncoding RNA,DNA methylation,and immune metabolism.Conclusion The studies in atherosclerotic genomics have gradually increased.
Atherosclerosis/genetics* ; Bibliometrics ; Biomarkers ; Genome-Wide Association Study ; Genomics ; Humans

Atherosclerosis is an important pathological basis for coronary artery disease. ANRIL is an antisense non-coding RNA located in Chr9p21 locus, which was identified as the most significant risk locus associated with atherosclerosis. ANRIL can produce multiple transcripts including linear and circular transcripts after various transcript splicing. It has been illustrated that ANRIL plays important roles in the pathology of atherosclerosis by regulating the proliferation and apoptosis of vascular cells. Linear ANRIL can regulate the proliferation of vascular smooth muscle cells (VSMCs) in plaques by chromatin modification, as well as influence the proliferation and the apoptosis of macrophages in post transcription; circular ANRIL can affect the proliferation and apoptosis of VSMCs by chromatin modification as well as interfering with rRNA maturation. In this review, we describe the ANRIL evolution, different transcripts characteristics, and their roles in the proliferation and apoptosis of vascular cells to participate in the process of atherosclerosis, for further understanding the pathogenesis of atherosclerosis and finding potential targets for diagnosis and treatment of atherosclerosis.
Apoptosis ; genetics ; Atherosclerosis ; genetics ; Cell Proliferation ; genetics ; Humans ; Myocytes, Smooth Muscle ; pathology ; RNA, Long Noncoding ; metabolism

To explore the correlation between the C807T polymorphism of platelet membrane glycoprotein I a (GP I a) gene and aspirin resistance in Chinese people, 200 patients with high-risk of atherosclerosis took aspirin (100 mg/d) for 7 days. Platelet aggregation function was detected using adenosine diphosphate (ADP) and arachidonic acid (AA) before and after the administration of aspirin. Then the subjects were divided into three groups according to the results of platelet aggregation function: an aspirin resistant (AR) group, an aspirin semi-responder (ASR) group and an aspirin-sensitive (AS) group. Platelet GP I a gene 807CT polymorphism was examined by means of polymerase chain reaction-sequence specific primers (PCR-SSP). The results showed that T allelic frequency in AR group and ASR group were higher that of AS group (P<0.005), and the prevalence of genotypes (TT+TC) of these two groups was significantly higher than that in AS group (P<0.05). Platelet GP I a T allele was significantly associated with aspirin resistance as revealed by multiple logistic regression (OR=3.76, 95% CI: 2.87-9.58). The results suggest that inherited platelet GP I a variations may have an important impact on aspirin resistance and the presence of GP I a T allele may be a marker of genetic susceptibility to aspirin resistance.
Aspirin/*administration & dosage ; Atherosclerosis/drug therapy ; Atherosclerosis/genetics ; Drug Resistance/*genetics ; Integrin alpha2/*genetics ; Platelet Aggregation Inhibitors/*administration & dosage ; Polymorphism, Genetic/*genetics

OBJECTIVEAngiotensin converting enzyme 2 (ACE2) efficiently hydrolyses the potent vasoconstrictor angiotensin II to vasodilative angiotensin (1-7). We hypothesized that ACE2 overexpression may inhibit inflammation response in atherosclerotic plaque by degrading Ang II into Ang-(1-7).

METHODSAtherosclerosis (AS) plaques were induced in the abdominal aorta of 38 rabbits by endothelial injury and atherogenic diet for 3 months. Rabbits were then underwent injection of a recombinant adenovirus (2.5 x 10(9) pfu/ml) carrying a murine ACE2 gene (Ad-ACE2) through a catheter into the abdominal aortic segments rich in plaques (n = 19) or injection of a control vector Ad-EGFP (n = 19). One month later, all rabbits were sacrificed and plaques from aortic segments were analyzed.

RESULTSACE2 expression in aortic tissues of the Ad-ACE2 group were confirmed by immunohistochemistry. Macrophage infiltration (13.6% +/- 4.2% vs. 23.6% +/- 6.9%, P < 0.01) and MCP-1 expression (13.2% +/- 0.4% vs. 25.0% +/- 7.4%, P < 0.01) were significantly reduced in Ad-ACE2 group compared to Ad-EGFP group.

CONCLUSIONSOverexpression of ACE2 inhibited atherosclerotic plaque inflammation response in hypercholesterolemic rabbits.

Animals ; Atherosclerosis ; genetics ; metabolism ; Cells, Cultured ; Diet, Atherogenic ; Genetic Vectors ; Peptidyl-Dipeptidase A ; genetics ; Rabbits ; Transfection

INTRODUCTION: The apolipoprotein E ( METHODS: We classified the RESULTS: The baseline serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly lower in carriers of CONCLUSION Polymorphism in the
Apolipoproteins E/genetics* ; Atherosclerosis/genetics* ; Cardiovascular Diseases ; Genotype ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use* ; Lipids

Adventitia ; Atherosclerosis/genetics* ; Cell Communication ; Humans ; Hyperhomocysteinemia/genetics* ; Sequence Analysis, RNA

In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS)-based liver metabolomics approach was used to explore the mechanism of "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in improving atherosclerosis(AS) of mice with apolipoprotein E gene knockout(ApoE~(-/-)). AS mouse model was induced by high-fat diet. The pathological and biochemical indexes such as the histopathological changes, body weight, liver weight, blood lipid level and inflammatory factors in the liver of mice were determined. The metabolic profiling of mice liver samples was performed with UPLC-Q-TOF-MS. Multiple statistical analysis methods including partial least squares discriminant analysis(PLS-DA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to screen and identify biomarkers. The levels of related enzymes including LCAT, sPLA2, EPT1 and ACER1 were detected. The results showed that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" significantly reduced the areas of aortic plaque and fat vacuoles of liver in AS mice and decreased the accumulation of lipid droplets and liver coefficient. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" also regulated the levels of blood lipid and inflammatory injury in the liver. The metabolites of the control group, the model group and the "Trichosanthis Fructus-Allii Macrostemonis Bulbus" group could be distinguished significantly. Fifteen potential biomarkers related to AS were discovered and preliminarily identified, seven of which could be regulated by "Trichosanthis Fructus-Allii Macrostemonis Bulbus" in a trend of returning to normal. Metabolic pathway analysis screened out two major metabolic pathways. "Trichosanthis Fructus-Allii Macrostemonis Bulbus" obviously regulated the levels of LCAT, sPLA2, EPT1 and ACER1. It was inferred that "Trichosanthis Fructus-Allii Macrostemonis Bulbus" could play a major role in AS treatment by regulating glycerophospholipid and sphingolipid metabolism disorders in the liver, with the mechanism probably relating to the intervention of the expression of LCAT, sPLA2, EPT1 and ACER1.
Animals ; Apolipoproteins E/genetics* ; Atherosclerosis/genetics* ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Liver ; Metabolomics ; Mice

Apolipoprotein A5 (Apo A5) is a novel member in apolipoprotein family, which is proven to be an important regulator in triglyceride metabolism, especially in adjusting the TG content in plasma. Apo A5 gene polymorphisms affect triglyceride metabolism and atherosclerotic cardiovascular diseases. The research focuses on -1131T>C, c.56C>G, and c.553G>T.
Apolipoprotein A-V ; genetics ; Atherosclerosis ; genetics ; Gene Frequency ; Humans ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide ; Triglycerides ; metabolism

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.
Animals ; Male ; Mice ; Atherosclerosis/genetics* ; Lipids ; Mice, Inbred C57BL ; Myocardial Infarction/genetics* ; RNA, Circular/genetics* ; RNA, Long Noncoding/genetics*