Circ_0104652 Promotes the Proliferation and Migration of ox-LDL-Stimulated Vascular Smooth Muscle Cells via Stabilizing ADAMTS7 and HMGB1.

BACKGROUND: Atherosclerosis (AS) stands as the primary contributor to cardiovascular disease, a pervasive global health concern. Extensive research has underscored the pivotal role of circular RNAs (circRNAs) in cardiovascular disease development. However, the specific functions of numerous circRNAs in AS remain poorly understood. METHODS: Quantitative real-time PCR analysis revealed a significant upregulation of circ_0104652 in oxidized low-density lipoprotein (ox-LDL)-induced vascular smooth muscle cells (VSMCs). Loss-of-function experiments were subsequently employed to assess the impact of circ_0104652 on ox-LDL-induced VSMCs. RESULTS: Silencing circ_0104652 was found to impede the proliferation and migration while promoting the apoptosis of ox-LDL-stimulated VSMCs. Mechanistic assays unveiled that circ_0104652 stabilized ADAM metallopeptidase with thrombospondin type 1 motif 7 (ADAMTS7) and high mobility group box 1 (HMGB1) by recruiting eukaryotic translation initiation factor 4A3 (EIF4A3) protein. Rescue assays further confirmed that circ_0104652 exerted its influence on ox-LDL-induced VSMC proliferation through modulation of ADAMTS7 and HMGB1. CONCLUSIONS: This study elucidates the role of the circ_0104652/EIF4A3/ADAMTS7/HMGB1 axis in ox-LDL-stimulated VSMCs, providing valuable insights into the intricate mechanisms involved.

The Association of ADAMTS7 Gene Polymorphisms with the Risk of Coronary Artery Disease Occurrence and Cardiovascular Survival in the Polish Population: A Case-Control and a Prospective Cohort Study.

The aim of this study was to investigate whether the polymorphisms of the ADAMTS7 gene affect the risk of occurrence and mortality due to CAD. The study group included 231 patients diagnosed with CAD and 240 control blood donors. The genotyping of specified polymorphisms, i.e., rs1994016, rs3825807, and rs7173743, was performed using the TaqMan-PCR. We found that the C allele carriers of the rs1994016 and A allele carriers of the rs3825807 polymorphisms increased the risk of CAD, respectively: OR = 1.72, p = 0.036; OR = 1.64, p = 0.04. Moreover, we studied the biological interactions of specified variants, i.e., rs3825807, rs1994016, and rs7173743, and previously approved risk factors of CAD. We demonstrated here that selected polymorphisms of ADAMTS7 increased the risk of CAD altogether with abnormalities of total cholesterol and LDL concentrations in serum. Although survival analyses did not reveal statistical significance, we observed a trend for the AA genotype of the rs3825807 ADAMTS7, which may predispose to death due to CAD in a 5-year follow-up. In conclusion, the ADAMTS7 polymorphisms investigated in this study may increase the risk of occurrence and/or death due to CAD in the Polish population.

BAY-9835: Discovery of the First Orally Bioavailable ADAMTS7 Inhibitor.

The matrix metalloprotease ADAMTS7 has been identified by multiple genome-wide association studies as being involved in the development of coronary artery disease. Subsequent research revealed the proteolytic function of the enzyme to be relevant for atherogenesis and restenosis after vessel injury. Based on a publicly known dual ADAMTS4/ADAMTS5 inhibitor, we have in silico designed an ADAMTS7 inhibitor of the catalytic domain, which served as a starting point for an optimization campaign. Initially our inhibitors suffered from low selectivity vs MMP12. An X-ray cocrystal structure inspired us to exploit amino acid differences in the binding site of MMP12 and ADAMTS7 to improve selectivity. Further optimization composed of employing 5-membered heteroaromatic groups as hydantoin substituents to become more potent on ADAMTS7. Finally, fine-tuning of DMPK properties yielded BAY-9835, the first orally bioavailable ADAMTS7 inhibitor. Further optimization to improve selectivity vs ADAMTS12 seems possible, and a respective starting point could be identified.

ADAMTS-7 Modulates Atherosclerotic Plaque Formation by Degradation of TIMP-1.

BACKGROUND: The ADAMTS7 locus was genome-wide significantly associated with coronary artery disease. Lack of the ECM (extracellular matrix) protease ADAMTS-7 (A disintegrin and metalloproteinase-7) was shown to reduce atherosclerotic plaque formation. Here, we sought to identify molecular mechanisms and downstream targets of ADAMTS-7 mediating the risk of atherosclerosis. METHODS: Targets of ADAMTS-7 were identified by high-resolution mass spectrometry of atherosclerotic plaques from Apoe-/- and Apoe-/-Adamts7-/- mice. ECM proteins were identified using solubility profiling. Putative targets were validated using immunofluorescence, in vitro degradation assays, coimmunoprecipitation, and Förster resonance energy transfer-based protein-protein interaction assays. ADAMTS7 expression was measured in fibrous caps of human carotid artery plaques. RESULTS: In humans, ADAMTS7 expression was higher in caps of unstable as compared to stable carotid plaques. Compared to Apoe-/- mice, atherosclerotic aortas of Apoe-/- mice lacking Adamts-7 (Apoe-/-Adamts7-/-) contained higher protein levels of Timp-1 (tissue inhibitor of metalloprotease-1). In coimmunoprecipitation experiments, the catalytic domain of ADAMTS-7 bound to TIMP-1, which was degraded in the presence of ADAMTS-7 in vitro. ADAMTS-7 reduced the inhibitory capacity of TIMP-1 at its canonical target MMP-9 (matrix metalloprotease-9). As a downstream mechanism, we investigated collagen content in plaques of Apoe-/- and Apoe-/-Adamts7-/- mice after a Western diet. Picrosirius red staining of the aortic root revealed less collagen as a readout of higher MMP-9 activity in Apoe-/- as compared to Apoe-/- Adamts7-/- mice. To facilitate high-throughput screening for ADAMTS-7 inhibitors with the aim of decreasing TIMP-1 degradation, we designed a Förster resonance energy transfer-based assay targeting the ADAMTS-7 catalytic site. CONCLUSIONS: ADAMTS-7, which is induced in unstable atherosclerotic plaques, decreases TIMP-1 stability reducing its inhibitory effect on MMP-9, which is known to promote collagen degradation and is likewise associated with coronary artery disease. Disrupting the interaction of ADAMTS-7 and TIMP-1 might be a strategy to increase collagen content and plaque stability for the reduction of atherosclerosis-related events.

ADAMTS7: a Novel Therapeutic Target in Atherosclerosis.

PURPOSE OF REVIEW: Genome-wide association studies have repeatedly linked the metalloproteinase ADAMTS7 to coronary artery disease. Here we aim to highlight recent findings surrounding the human genetics of ADAMTS7, novel mouse models that investigate ADAMTS7 function, and potential substrates of ADAMTS7 cleavage. RECENT FINDINGS: Recent genome-wide association studies in coronary artery disease have replicated the GWAS signal for ADAMTS7 and shown that the signal holds true even across different ethnic groups. However, the direction of effect in humans remains unclear. A recent novel mouse model revealed that the proatherogenicity of ADAMTS7 is derived from its catalytic functions, while at the translational level, vaccinating mice against ADAMTS7 reduced atherosclerosis. Finally, in vitro proteomics approaches have identified extracellular matrix proteins as candidate substrates that may be causal for the proatherogenicity of ADAMTS7. ADAMTS7 represents an enticing target for therapeutic intervention. The recent studies highlighted here have replicated prior findings, confirming the genetic link between ADAMTS7 and atherosclerosis, while providing further evidence in mice that ADAMTS7 is a targetable proatherogenic enzyme.

The rs3825807 Polymorphism of ADAMTS7 as a Potential Genetic Marker for Myocardial Infarction in Slovenian Subjects with Type 2 Diabetes Mellitus.

BACKGROUND: A disintegrin and metalloprotease with thrombospondin motif 7 (ADAMTS-7) was reported to play a role in the migration of vascular smooth muscle cells and neointimal formation. The object of the study was to investigate the association between the rs3825807 polymorphism of ADAMTS7 and myocardial infarction among patients with type 2 diabetes mellitus in a Slovenian cohort. METHODS: 1590 Slovenian patients with type 2 diabetes mellitus were enrolled in this retrospective cross-sectional case-control study. In total, 463 had a history of recent myocardial infarction, and 1127 of the subjects in the control group had no clinical signs of coronary artery disease. Genetic analysis of an rs3825807 polymorphism of ADAMTS7 was performed with logistic regression. RESULTS: Patients with the AA genotype had a higher prevalence of myocardial infarction than those in the control group in recessive [odds ratio (OR) 1.647; confidence interval (CI) 1.120-2.407; p = 0.011] and co-dominant (OR 2.153; CI 1.215-3.968; p = 0.011) genetic models. CONCLUSION: We found a statistically significant association between rs3825807 and myocardial infarction in a cohort of Slovenian patients with type 2 diabetes mellitus. We report that the AA genotype might be a genetic risk factor for myocardial infarction.

Genome-wide meta-analysis identifies new candidate genes for sickle cell disease nephropathy.

Sickle cell disease nephropathy (SCDN), a common SCD complication, is strongly associated with mortality. Polygenic risk scores calculated from recent transethnic meta-analyses of urinary albumin-to-creatinine ratio and estimated glomerular filtration rate (eGFR) trended toward association with proteinuria and eGFR in SCD but the model fit was poor (R2 < 0.01), suggesting that there are likely unique genetic risk factors for SCDN. Therefore, we performed genome-wide association studies (GWAS) for 2 critical manifestations of SCDN, proteinuria and decreased eGFR, in 2 well-characterized adult SCD cohorts, representing, to the best of our knowledge, the largest SCDN sample to date. Meta-analysis identified 6 genome-wide significant associations (false discovery rate, q ≤ 0.05): 3 for proteinuria (CRYL1, VWF, and ADAMTS7) and 3 for eGFR (LRP1B, linc02288, and FPGT-TNNI3K/TNNI3K). These associations are independent of APOL1 risk and represent novel SCDN loci, many with evidence for regulatory function. Moreover, GWAS SNPs in CRYL1, VWF, ADAMTS7, and linc02288 are associated with gene expression in kidney and pathways important to both renal function and SCD biology, supporting the hypothesis that SCDN pathophysiology is distinct from other forms of kidney disease. Together, these findings provide new targets for functional follow-up that could be tested prospectively and potentially used to identify patients with SCD who are at risk, before onset of kidney dysfunction.

Long non­coding RNA LINC01960­201 hinders decidualization of endometrial stromal cell in endometriosis: Relevance to endometrial receptivity.

Emerging data have indicated that long non­coding RNAs (lncRNA) are associated with the pathogenesis of endometriosis. However, few are associated with endometriosis­associated infertility. In addition, to the best of our knowledge, the role of lncRNAs in decidual formation during the window of implantation with endometriosis has not been reported to date. Based on our previous results, the aim of the present study was to explore the role of lncRNA long intergenic non­protein coding RNA (LINC)01960­201 in in vitro decidualization of endometrial stromal cells in endometriosis during the window of implantation, as well as to explore the biological function of LINC01960­201, and the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 7 (ADAMTS7), hsa­microRNA (miR)­760 and hsa­miR­608 in the decidualization of endometrial stromal cells with endometriosis. Using miRanda, PITA and RNAhybrid, the present study predicted which miRs share the common target gene ADAMTS7 with LINC01960­201 and the existence of regulatory targets. Dual luciferase vectors were constructed to extract the plasmids and measure the relative fluorescence values in order to estimate target regulatory association between LINC01960­201, ADAMTS7 and miRs. Mid­secretory endometrial tissues were collected from women with endometriosis­associated infertility. From these tissues, endometrial stromal cells were extracted and cultured as primary cultures. Medroxyprogesterone acetate (MPA) and 8­Bromoadenosine 3',5'­cyclic monophosphate (8­Br­cAMP) were added to induce in vitro decidualization, and to knockdown LINC01960­201 and transfect a hsa­miR­608 mimic at the same time. Reverse transcription­quantitative PCR and western blotting were conducted to compare the difference in gene expression between the experimental and negative control groups. No regulatory sites between LINC01960­201 and hsa­miR­608 were identified; however, potential regulatory sites were detected between hsa­miR­608 and the 3'­untranslated region (UTR) of ADAMTS7, whereas neither the 3'­UTR of LINC01960­201 or the 3'­UTR of ADAMTS7 had any regulatory targets with hsa­miR­760. During the process of decidualization of endometrial stromal cells by in vitro induction, the expression of hsa­miR­608 in the knockdown group was significantly higher compared with that of the negative control group after LINC01960­201­knockdown, and the expression of ADAMTS7 in the transfection group was significantly lower compared with that of the negative control group after hsa­miR­608 mimic transfection. In conclusion, it was hypothesized that LINC01960­201 played a notable regulatory role in the decidualization of endometrial stromal cells in women with endometriosis during the window of implantation, and its abnormal expression may lead to the decline of endometrial receptivity and recurrent abortions.

Genome-wide pleiotropy analysis of coronary artery disease and pneumonia identifies shared immune pathways.

Coronary artery disease (CAD) remains the leading cause of death despite scientific advances. Elucidating shared CAD/pneumonia pathways may reveal novel insights regarding CAD pathways. We performed genome-wide pleiotropy analyses of CAD and pneumonia, examined the causal effects of the expression of genes near independently replicated SNPs and interacting genes with CAD and pneumonia, and tested interactions between disruptive coding mutations of each pleiotropic gene and smoking status on CAD and pneumonia risks. Identified pleiotropic SNPs were annotated to ADAMTS7 and IL6R. Increased ADAMTS7 expression across tissues consistently showed decreased risk for CAD and increased risk for pneumonia; increased IL6R expression showed increased risk for CAD and decreased risk for pneumonia. We similarly observed opposing CAD/pneumonia effects for NLRP3. Reduced ADAMTS7 expression conferred a reduced CAD risk without increased pneumonia risk only among never-smokers. Genetic immune-inflammatory axes of CAD linked to respiratory infections implicate ADAMTS7 and IL6R, and related genes.

Coronary Disease Association With ADAMTS7 Is Due to Protease Activity.

[Figure: see text].

Age-associated changes in the transcriptomes of non-cultured adipose-derived stem cells from young and old mice assessed via single-cell transcriptome analysis.

Adipose-derived stem cells (ASCs) exhibit self-renewal and pluripotency. The differentiation potency of ASCs has been reported to deteriorate with aging; however, relevant studies used ASCs that were isolated and subcultured several times. It is still unclear whether subcultured ASCs accurately reflect the in vivo state. To address this question, we used freshly isolated stromal vascular fractions (SVFs) and performed comprehensive single-cell transcriptome analysis. In this study, we identified three cell populations as putative ASC candidates in SVFs and three novel ASC-related genes: Adamts7, Snai2, and Tgfbr1, that are reported to be negative regulators of cell differentiation. Moreover, we identified age-associated high gene expression levels of Adamts7, Egfr, and Igfbp4 in the earliest differentiation stage of ASCs. These results suggest that aging may make it impossible to maintain the stringency of the regulation of the expression of some genes related to ASC differentiation.

Association of polymorphisms in ADAMTS-7 gene with the susceptibility to coronary artery disease - a systematic review and meta-analysis.

OBJECTIVE: To systematically review literature evidence to discover the association of ADAMTS7 (A Disintegrin And Metalloproteinase with Thrombospondin-like motifs 7) polymorphisms and the risk of developing CAD (coronary artery disease). DATA SOURCES: A related literature search in online databases, including EMBASE, PubMed, and Web of Science was undertaken. The period covered was from 2007 to September 10, 2019. RESULTS: Of 256 citations retrieved, nine relevant studies were selected for detailed evaluation. Five SNPs (rs3825807, rs1994016, rs4380028, rs79265682, and rs28455815) in ADAMTS7 gene were identified among included studies. There were 51,851 cases and 89,998 controls included in four studies for SNP rs3825807, 13,403 cases and 11,381 controls included in two studies for SNP rs1994016, 37,838 cases and 38,245 controls included in two studies for SNP rs4380028, 3,133 cases and 5,423 controls included in one study for SNP rs79265682, 103,494 cases and 198,684 controls included in one study for SNP rs28455815. We found most consistent evidence for an association with CAD on coronary angiogram with ADAMTS7 SNP rs3825807 risk allele A in contrast to control G allele, followed by rs4380028 (C vs. T allele), and rs1994016 (C vs. T allele). CONCLUSIONS: ADAMTS7 polymorphism is likely an important risk factor for development of CAD. Our data also suggest that the ADAMTS7 polymorphism may be a risk factor for CAD progression in patients who already have pathology in their coronary arteries. REVIEW METHODS: We included all studies in English language that reported correlation between the ADAMTS7 polymorphism and CAD in human cases.

Hypomethylation of DNA promoter upregulates ADAMTS7 and contributes to HTR-8/SVneo and JEG-3 cells abnormalities in pre-eclampsia.

INTRODUCTION: Accumulating evidences have suggested a crucial role of epigenetics in the initiation and progression of pre-eclampsia (PE). Here, we studied the expression of the metalloproteinase ADAMTS7 and the methylation level of its promoter in PE placentas and investigated ADAMTS7 role in the pathogenesis of PE. METHODS: We first explored ADAMTS7 expression in PE and normal placentas by reverse transcription quantitative PCR (RT-qPCR), western blot, and immunohistochemistry. Methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to evaluate the methylation status of ADAMTS7 promoter. Treatment with 5'-Aza was used to induce demethylation and thereby to explore the direct relationship between promoter methylation and ADAMTS7 expression. CCK8 assay, colony formation assay, and trans-well assay were conducted to assess the viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells. RESULTS: Our results showed that ADAMTS7 expression was upregulated in PE placentas. Methylation analysis revealed a hypomethylated status of ADAMTS7 promoter regions in PE placenta tissues. Besides, demethylation induced by 5'-Aza directly restored ADAMTS7 expression in trophoblast cells. Finally, overexpression of ADAMTS7 inhibited viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells, while silence of ADAMTS7 by RNA interference reciprocally facilitated cell viability, migration and invasion in vitro. DISCUSSION: Upregulation of ADAMTS7 by promoter hypomethylation in placenta might contribute to the etiology of PE via suppressing cell functions of trophoblasts.

Effect of a coronary-heart-disease-associated variant of ADAMTS7 on endothelial cell angiogenesis.

BACKGROUND AND AIMS: Recent studies have unveiled an association between ADAMTS7 gene variation and coronary artery disease (CAD) caused by atherosclerosis. We investigated if the ADAMTS7 Serine214-to-Proline substitution arising from a CAD-associated variant affected angiogenesis, since neovascularization plays an important role in atherosclerosis. METHODS AND RESULTS: ADAMTS7 knockdown in vascular endothelial cells (ECs) attenuated their angiogenesis potential, whereas augmented ADAMTS7-Ser214 expression had the opposite effect, leading to increased ECs migratory and tube formation ability. Proteomics analysis showed an increase in thrombospondin-1, a reported angiogenesis inhibitor, in culture media conditioned by ECs with ADAMTS7 knockdown and a decrease of thrombospondin-1 in media conditioned by ECs with ADAMTS7-Ser214 overexpression. Cleavage assay indicated that ADAMTS7 possessed thrombospondin-1 degrading activity, which was reduced by the Ser214-to-Pro substitution. The pro-angiogenic effect of ADAMTS7-Ser214 diminished in the presence of a thrombospondin-1 blocking antibody. CONCLUSIONS: The ADAMTS7 Ser217-to-Pro substitution as a result of ADAMTS7 polymorphism affects thrombospondin-1 degradation, thereby promoting atherogenesis through increased EC migration and tube formation.

Upregulation of miR­423 improves autologous vein graft restenosis via targeting ADAMTS­7.

Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR­423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs­7 (ADAMTS­7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR­423 target, ADAMTS­7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR­423 in plasma of patients with CHD prior to and following CABG confirms that miR­423 may be a suitable target for preventing VGF. Furthermore, a dual­luciferase reporter gene assay indicated that miR­423 directly interacted with ADAMTS­7 and suppressed its expression. Ectopic expression of miR­423 suppressed ADAMTS­7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS­7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR­423 also enhanced re­endothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR­423/ADAMTS­7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.

ADAMTS7: Recombinant Protein Expression and Purification.

ADAMTS7 is a secreted protease that is predominantly expressed in tissues of the cardiovascular system and tendon. Although recent evidence suggests that it may play a role in the etiology of coronary artery disease, its physiological function and substrates are unknown. The enzyme undergoes extensive posttranslational modifications, including chondroitin sulfate attachment, N and O-linked glycosylation, and a two-step activation process. For the benefit of scientists who study the function of ADAMTS7 and its role in disease, this chapter provides an introduction to the chemical and functional properties of the various ADAMTS7 domains, as well as a protocol for the recombinant expression and purification of ADAMTS7.

ADAMTS7 and ZC3HC1 Share Genetic Predisposition to Coronary Artery Disease and Large Artery Ischemic Stroke.

Coronary artery disease (CAD) and ischemic stroke (IS) are commonly considered distinct disease phenotypes. However, there is some evidence in favor of a degree of overlap between genetic susceptibility to CAD and genetic risk factors for IS. In the present study, we aimed to examine the role of two single-nucleotide polymorphisms (SNPs), rs3825807 and rs11556924, located in the ADAMTS7 and ZC3HC1 genes, respectively, associated with CAD in published GWASs in European populations and their possible contribution to the development of coronary atherosclerosis and cerebral LA atherosclerosis in a case-control study of an the Iranian population. The sample size was 400, and the methodology for SNP genotyping was ARMS-PCR. Both SNPs showed strong associations with CAD in the analyses comparing significant CAD and myocardial infarction (MI) with controls. None of them, however, were associated with MI in patients with significant CAD. Our findings further support the role of the ADAMTS7 locus in promoting atherosclerosis in LAs of the brain. Regarding ZC3HC1 rs11556924, our study further supports the observed association of rs11556924 with LA IS coming from previous GWASs. In conclusion, the data showed that common variants in ADAMTS7 and ZC3HC1 genes contribute to an increased risk for both CAD and LA (atherosclerotic) IS.

lncRNA/mRNA profiling of endometriosis rat uterine tissues during the implantation window.

Endometriosis is associated with changes in long non­coding RNA (lncRNA) and mRNA expression, but the exact changes during the implantation window are unknown. Therefore, this study aimed to explore the lncRNA and mRNA expression profiles in the uterus of rats with endometriosis during the implantation window. A total of 35 non­pregnant female rats were randomized to the endometriosis (n=13), adipose tissue control (n=8) and blank control (n=14) groups. On the 5th day of pregnancy, the rats were sacrificed to obtain uterine tissues. lncRNA and mRNA were analyzed using gene chips. A total of five differentially expressed lncRNA and four mRNA were validated by reverse transcription­quantitative (RT­q)PCR. Immunohistochemistry and western blotting were used to determine the expression of the ADAM metallopeptidase with thrombospondin type 1 motif 7 (Adamts7), tumor protein p53 (Tp53), distal­less homeobox 3 (Dlx3) and pyrimidinergic receptor P2Y6 (P2ry6) proteins. There were 115 upregulated lncRNAs, 51 downregulated lncRNAs, 97 upregulated mRNAs and 85 downregulated mRNAs in the endometriosis group. RT­qPCR confirmed the trends for five lncRNAs and four mRNAs (Adamts7, Tp53, Dlx3 and P2ry6). The relative protein expression levels of Adamts7, P2ry6, Dlx3 and TP53 were significantly different in the endometriosis group (P<0.05 vs. controls). Bioinformatics predicted the co­expression relationship of the selected five lncRNA and four mRNA. Gene ontology and the Kyoto Encyclopedia of Genes and Genomes predicted that Adamts7, P2ry6, Dlx3 and TP53 were involved in endometriosis­related inflammation and reproductive pathways. In conclusion, the changes in the expression of lncRNAs, mRNAs and proteins (Adamts7, P2ry6, Dlx3 and TP53) may possibly affect endometrial receptivity in rats with endometriosis during the implantation window, probably resulting in implantation failure of the embryo.