Medicine for treating atherosclerosis caused by high fat diet

Abstract

The invention discloses a medicine for treating atherosclerosis caused by high fat diet, and belongs to the technical field of cardiovascular disease treatment. According to the pharmaceutical composition, siRNA (small interfering Ribonucleic Acid) capable of inhibiting expression of LncRNA-ENST00000564510.1 in a targeted manner is used as a core active component, and is combined with a delivery system for use. Animal experiments prove that the siRNA injection medicine can remarkably reduce the aortic plaque area of an atherosclerosis model mouse and effectively improve the levels of serum total cholesterol, triglyceride and low-density lipoprotein cholesterol. Meanwhile, the medicine can remarkably inhibit secretion of vascular endothelial cell inflammatory factors induced by ox-LDL, and the cell activity is improved. Therefore, the invention provides a novel therapeutic drug based on lncRNA targeted regulation, and the novel therapeutic drug has an excellent anti-atherosclerosis effect.

Description

Technical Field

[0001] The present invention belongs to the technical field of cardiovascular disease treatment, and in particular relates to a medicine for treating atherosclerosis caused by a high-fat diet. Background Art

[0002] Atherosclerosis (AS) is a chronic, progressive inflammatory disease that primarily affects large and medium-sized arteries. Its pathological characteristics are lipid deposition in the arterial intima, smooth muscle cell proliferation, foam cell formation, and fibrosis, ultimately leading to the formation of atherosclerotic plaques and vascular stenosis. In severe cases, it can cause fatal cardiovascular events such as thrombosis, myocardial infarction, and stroke. The development and progression of AS is closely associated with multiple risk factors, including hyperlipidemia, hypertension, diabetes, smoking, obesity, and genetic factors.

[0003] In recent years, changes in lifestyle have led to a continued rise in the prevalence of atherosclerosis-related diseases worldwide. Due to factors such as dietary changes, reduced physical activity, and increased social pressure, the prevalence and mortality rates of atherosclerosis have been increasing year by year, posing a significant challenge to public health systems.

[0004] Currently, the main clinical treatments for atherosclerosis include lifestyle interventions, lipid-lowering medications, anti-inflammatory therapies, interventional procedures, and surgical interventions. Although lipid-lowering therapies such as statins can slow disease progression to a certain extent, some patients still experience poor efficacy, drug resistance, or adverse reactions. Therefore, developing a novel, safe, and precise drug for the treatment of atherosclerosis has important clinical and social implications for improving patient prognosis and reducing the burden of disease. Summary of the Invention

[0005] The purpose of the present invention is to provide a highly effective and targeted drug for treating atherosclerosis caused by a high-fat diet.

[0006] To achieve the above object, the present invention provides the following technical solutions: In a first aspect, the present invention provides a drug for treating atherosclerosis caused by a high-fat diet, the drug comprising an inhibitor that targets and inhibits the expression of LncRNA-ENST00000564510.1 and a drug delivery vector; The transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1.

[0007] Preferably, the inhibitor is a siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.11.

[0008] Preferably, the concentration of the inhibitor in the drug is 200 μg / mL-1000 μg / mL.

[0009] Preferably, the drug delivery carrier is one of liposomes, polyethyleneimine and its derivatives, nanoparticles or cationic lipid complexes.

[0010] Preferably, the drug delivery carrier is polyethyleneimine and its derivatives.

[0011] In a second aspect, the present invention provides an inhibitor targeting the inhibition of LncRNA-ENST00000564510.1 expression in the preparation of a drug for treating atherosclerosis caused by a high-fat diet, wherein the transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1.

[0012] Preferably, the inhibitor is a siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.11.

[0013] In a third aspect, the present invention provides a use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for improving dyslipidemia caused by a high-fat diet, wherein the transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1; The inhibitor is a siRNA comprising a sense strand shown in SEQ ID NO.10 and an antisense strand shown in SEQ ID NO.11; The dyslipidemia is abnormally elevated total cholesterol, triglycerides and low-density lipoprotein cholesterol.

[0014] In a fourth aspect, the present invention provides a use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for improving vascular endothelial cell damage caused by a high-fat diet, wherein the transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1; The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.11.

[0015] In a fifth aspect, the present invention provides a method for preparing a drug for improving vascular inflammatory response induced by a high-fat diet by targeting an inhibitor of LncRNA-ENST00000564510.1 expression, wherein the transcript sequence of the LncRNA-ENST00000564510.1 is as shown in SEQ ID NO. 1; The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.11.

[0016] Preferably, the inflammatory response is an abnormal increase in TNF-α and IL-6.

[0017] The beneficial effects of the present invention are: This paper first reveals that LncRNA-ENST00000564510.1 (SEQ ID NO.1) is specifically highly expressed in high-fat diet-induced atherosclerosis ( Figure 1-2 ), precise silencing of the target was achieved through specific siRNA inhibitors (SEQ ID NO.10-11) ( Figure 3 ), breaking through the side effects caused by the multi-target effects of traditional lipid-lowering drugs.

[0018] Secondly, LncRNA-ENST00000564510.1 inhibitory drugs have multiple synergistic therapeutic mechanisms: inhibiting this lncRNA can increase the survival rate of vascular endothelial cells damaged by ox-LDL, reduce the secretion levels of pro-inflammatory factors TNF-α and IL-6, and reduce serum TC, TG, and LDL-C levels, thereby achieving efficient treatment of atherosclerosis caused by a high-fat diet. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Comparison of the expression levels of LncRNA-ENST00000564510.1 (a), LncRNA-ENST00000569849.1 (b), and LncRNA-ENST00000449672 (c) in carotid artery plaque tissues and control tissues; Figure 2 The relative expression levels of LncRNA-ENST00000564510.1, LncRNA-ENST00000569849.1, and LncRNA-ENST00000449672 in the ox-LDL-induced HCAEC atherosclerosis model were detected. Figure 3 Results of verification of the interference efficiency of siRNA-a (a) and siRNA-b (b) designed for the present invention; Figure 4 Figure 2 is the test result of cell survival rate in different treatment groups; Figure 5 Figure 2 is the detection result of TNF-α and IL-6 content in the cell supernatant of different treatment groups; Figure 6 This is the result of testing the therapeutic effect on mice with atherosclerosis; in, Figure 6 (a) Comparison of the expression levels of LncRNA-ENST00000564510.1 in the aorta of mice in each group; Figure 6 (b) The test results of TC (total cholesterol) levels in the serum of mice in each group; Figure 6 (c) Detection results of TG (triglyceride) levels in the serum of mice in each group; Figure 6 (d) is the test results of LDL-C (low-density lipoprotein cholesterol) levels in the serum of mice in each group; Figure 6 (e) The detection results of aortic plaque area in each group of mice. DETAILED DESCRIPTION

[0020] Long non-coding RNA (lncRNA) is a class of RNA molecules longer than 200 nucleotides that do not encode proteins but have important regulatory functions. A growing body of research indicates that lncRNAs play a crucial role in various physiological and pathological processes, particularly in the pathogenesis of cardiovascular disease. Therefore, this study aimed to identify lncRNAs involved in ox-LDL-induced atherosclerosis, thereby providing new avenues for the precision treatment of atherosclerosis. Based on the regulatory role of lncRNAs in cardiovascular disease, the present study identified LNCRNA-ENST00000564510.1 through screening, which was significantly overexpressed in a high-fat diet-induced atherosclerosis model. This led to the development of a therapeutic drug targeting this lncRNA.

[0021] Example 1 Screening for differentially expressed lncRNAs in the process of ox-LDL-induced atherosclerosis (1) Searching for potentially differentially expressed LncRNAs Arterial plaques are the specific manifestation of atherosclerosis in local blood vessels. Therefore, the present invention attempts to identify lncRNAs that may be involved in the regulation of atherosclerosis from lncRNAs differentially expressed in arterial plaques.

[0022] This study screened three LncRNAs that are highly expressed in arterial plaques from the GEO (Gene Expression Omnibus) database. The numbers and gene sequences of the three genes in the GSE207252 dataset are as follows: The lncRNA gene corresponding to TC1600002152.oe.1 is LncRNA-ENST00000564510.1, and its transcript sequence is shown in SEQ ID NO.1; The lncRNA gene corresponding to TC0800002158.oe.1 is lncRNA-ENST00000569849.1, and its transcript sequence is shown in SEQ ID NO.2; The lncRNA gene corresponding to TC07001286.hg.4 is lncRNA-ENST00000449672, and its transcript sequence is shown in SEQ ID NO.3.

[0023] The differential expression of the three genes in 4 carotid artery plaque specimens and the vascular tissue control group 1 cm away from the plaque is shown in the figure. Figure 1 shown.

[0024] As can be seen from the figure, the expression levels of LncRNA-ENST00000564510.1, LncRNA-ENST00000569849.1 and LncRNA-ENST00000449672 in carotid artery plaque specimens were significantly higher than those in the control group.

[0025] (2) Detection of lncRNAs highly expressed in ox-LDL-induced atherosclerosis cell models 1. The primer sequences designed based on the transcript sequences of LncRNA-ENST00000564510.1, LncRNA-ENST00000569849.1, and LncRNA-ENST00000449672 are as follows: The primer sequences designed based on the transcript sequence of LncRNA-ENST00000564510.1 are as follows: Upstream primer: 5′-GACAAGGACCCACTGTCTGG-3′, SEQ ID NO. 4; Downstream primer: 5'-ACTTCGAGCAGCAGTTCTCC-3', SEQ ID NO. 5; The primer sequences designed based on the transcript sequence of LncRNA-ENST00000569849.1 are as follows: Upstream primer: 5′-TCTGCCACAAAGTGAGACCC-3′, SEQ ID NO. 6; Downstream primer: 5′-CAGTTATCCCTGCAGCCACC-3′, SEQ ID NO. 7; The primer sequences designed based on the transcript sequence of LncRNA-ENST00000449672 are as follows: Upstream primer: 5′-TGGTGCTCCCACAAGAAAGG-3′, SEQ ID NO. 8; Downstream primer: 5′-GTTCCTCCTGCTTTCTGCCT-3′, SEQ ID NO. 9; The primers were synthesized by Shanghai Sangon Biotechnology Co., Ltd.

[0026] 2. HCAEC cells (human coronary artery endothelial cells) were seeded into 6-well culture dishes and cultured in EGM-2 complete medium until the cell density reached above 80%.

[0027] 3. Establish an atherosclerosis cell model according to the following components Control group (Con group): No ox-LDL treatment was added, and new EGM-2 complete medium (2 mL, the same below) was added for 24 hours; Experimental group (ox-LDL treatment group): EGM-2 complete medium containing a final concentration of 100 μg / mL ox-LDL was added for 24 hours.

[0028] 4. Aspirate the culture medium, wash the cells twice with PBS, add 1 mL of TRIzol to lyse the cells, and extract total RNA according to the manufacturer's instructions; After the RNA purity and concentration were tested using NanoDrop, the RNA was reverse transcribed into cDNA using a reverse transcription kit.

[0029] 5. Prepare the reaction system according to the SYBR Green PCR Master Mix instructions: 2 μL of cDNA template, 0.4 μL of upstream primer (10 μM), 0.4 μL of downstream primer (10 μM), 10 μL of SYBR Green PCR Master Mix (2×), and RNase-free ddH2O to make up to 20 μL.

[0030] 6. Carry out the reaction according to the following reaction procedure: Pre-denaturation at 95°C for 10 minutes, 1 cycle; denaturation at 95°C for 15 seconds, annealing / extension at 60°C for 1 minute, 35 cycles; 7. GAPDH was used as the internal reference gene and data analysis was performed using 2 ⁻ΔΔCt The relative expression levels of each lncRNA in the ox-LDL treatment group and the control group were compared using the method, and five biological replicates were set for each group.

[0031] The test results are shown in Figure 2 In, from Figure 2 The results show that compared to the Con group, the relative gene expression levels of LncRNA-ENST00000564510.1 and LncRNA-ENST00000449672 were significantly increased in the ox-LDL-treated group, while the relative gene expression level of LncRNA-ENST00000569849.1 did not change significantly. This may be because arterial plaques involve multiple cell types and different regulatory mechanisms, and LncRNA-ENST00000569849.1 may not be involved in the process of ox-LDL-induced arteriosclerosis. In subsequent experiments, only LncRNA-ENST00000564510.1 and LncRNA-ENST00000449672 will be selected for subsequent experiments.

[0032] Example 2 Detect whether inhibition of differentially expressed LncRNA can inhibit the decrease in vascular endothelial cell activity caused by oxidized low-density lipoprotein (ox-LDL) (1) Design and verify siRNA targeting lncRNA 1. siRNA Design The sequence of siRNA-a (synthesized by Shanghai Sangon Biotechnology) designed based on the transcript sequence of LncRNA-ENST00000564510.1 is as follows: Sense strand: 5′-AUUGGAAUCUCUGAAGAUGGG-3′, SEQ ID NO. 10; Antisense strand: 5'-CAUCUUCAGAGAUUCCAAUAG-3', SEQ ID NO. 11; The siRNA-b sequence designed based on the transcript sequence of LncRNA-ENST00000449672 is as follows: Sense strand: 5′-AGAUAACUUGCAUUAAGCGAG-3′, SEQ ID NO. 12; Antisense strand: 5'-CGCUUAAUGCAAGUUAUCUGG-3', SEQ ID NO.13.

[0033] 2. Interference effect verification HCAEC cells were seeded into 6-well plates and cultured with EGM-2 complete medium until the cell confluence reached 60%–70% before transfection. Prepare siRNA-lipo mixture according to the Lipofectamine RNAiMAX instructions (final siRNA concentration 50 nM), add the mixture to the cells, and transfect for 48 hours. The control group was transfected with NC-siRNA as a control; Subsequently, referring to the method of Example 1, the expression of LncRNA-ENST00000564510.1 and LncRNA-ENST00000449672 after siRNA transfection was detected.

[0034] The results obtained are as follows Figure 3 As shown in the figure, it can be seen that siRNA-a can effectively inhibit the expression of LncRNA-ENST00000564510.1 in vascular endothelial cells. At the same time, siRNA-b can effectively inhibit the expression of LncRNA-ENST00000449672 in vascular endothelial cells, indicating that both siRNAs designed in the present invention can effectively exert inhibitory effects.

[0035] (2) Detect the effects of inhibiting LncRNA-ENST00000564510.1 or LncRNA-ENST00000449672 on ox-LDL-induced vascular endothelial cell death 1. Seed approximately 5,000 HCAEC cells per well in a 96-well plate and add 100 μL of EGM-2 complete medium. Culture cells until they reach 60%–70% confluency and prepare for transfection.

[0036] 2. Prepare siRNA-lipo mixture of siRNA-a or siRNA-b according to the instructions of Lipofectamine RNAiMAX (final siRNA concentration: 50 nM), add the mixture to the cells, and transfect for 48 hours; 3. Treat the cells according to the following groups: Control group: transfected with NC-siRNA, replaced with new EGM-2 complete medium (100 μL), and cultured for another 24 h; ox-LDL treatment group: transfected with NC-siRNA, replaced with EGM-2 complete medium containing a final concentration of 100 μg / mL ox-LDL, and cultured for another 24 h; Interference group a: transfected with siRNA-a, replaced with EGM-2 complete medium containing a final concentration of 100 μg / mL ox-LDL, and cultured for another 24 h; Interference group b: transfected with siRNA-b, replaced with EGM-2 complete medium containing a final concentration of 100 μg / mL ox-LDL, and cultured for 24 h. Five biological replicates were set for each group.

[0037] 4. After the incubation period, add 10 μL of CCK-8 solution to each well and incubate at 37°C for 3 hours. Measure the absorbance at OD450nm using a microplate reader to calculate the cell viability.

[0038] from Figure 4 The results show that the survival rate of HCAEC cells in the model group after ox-LDL treatment was significantly reduced, indicating that the ox-LDL-induced atherosclerosis cell model constructed in the present invention was successfully constructed.

[0039] Compared with the model group, the cell survival rate in interference group a was significantly increased, while the cell survival rate in interference group b, although slightly higher than that of the model group, did not meet the statistical requirements. This result indicates that the use of siRNA-a to inhibit LncRNA-ENST00000564510.1 can effectively improve the ox-LDL-induced decrease in vascular endothelial cell activity. However, the use of siRNA-b to inhibit LncRNA-ENST00000449672 was unable to effectively improve the ox-LDL-induced decrease in vascular endothelial cell activity. This may be because, although LncRNA-ENST00000449672 is highly expressed, it is only a high expression marker and is not involved in the physiological process of ox-LDL-induced decrease in activity.

[0040] Example 3 Detect the effect of inhibiting LncRNA-ENST00000564510.1 on the abnormal secretion of proinflammatory factors in vascular endothelial cells caused by ox-LDL 1. HCAEC cells were seeded into 6-well plates and cultured with EGM-2 complete medium until the cell confluence reached 60%–70% before transfection. The siRNA-lipo mixture of siRNA-a (final siRNA concentration: 50 nM) was prepared according to the instructions of Lipofectamine RNAiMAX (Invitrogen), and the mixture was added to the cells for transfection for 48 h. The control group was transfected with NC-siRNA as a control.

[0041] 2. Treat the cells according to the following groups: Control group: transfected with NC-siRNA, replaced with fresh EGM-2 serum-free medium (2 mL), and cultured for another 24 h; ox-LDL treatment group: transfected with NC-siRNA, replaced with EGM-2 serum-free medium containing a final concentration of 100 μg / mL ox-LDL, and cultured for another 24 h; Interference group a: transfected with siRNA-a, replaced with EGM-2 serum-free medium containing a final concentration of 100 μg / mL ox-LDL, and cultured for another 24 h; 3. The culture supernatant of each treatment group was collected and the TNF-α and IL-6 levels in the supernatant of each treatment group were determined according to the instructions of the TNF-α ELISA kit and IL-6 ELISA kit (both purchased from Beyotime Biotechnology Co., Ltd.).

[0042] from Figure 5 The results show that compared with the ox-LDL treatment group, the levels of TNF-α and IL-6 in the supernatant of interference group a were significantly reduced, indicating that inhibiting LncRNA-ENST00000564510.1 through siRNA-a can effectively inhibit the abnormal secretion of proinflammatory factors in vascular endothelial cells caused by ox-LDL, thereby helping to treat atherosclerosis caused by ox-LDL.

[0043] Example 4 (1) Construction of mouse atherosclerosis model Sixteen 8-week-old ApoE− / − mice were randomly divided into two groups: a model group and a treatment group. Both groups of mice were fed a high-fat diet containing 2% cholesterol for 12 weeks to establish an atherosclerosis model (mice were purchased from Beijing Weitong Lihua Laboratory Animal Technology Co., Ltd.); Eight wild-type C57BL / 6J mice were fed a normal diet without cholesterol (with the same ingredients except for the cholesterol content) under the same conditions as the model group and treatment group for 12 weeks and served as the control group.

[0044] (2) Drug preparation Prepare siRNA injection drugs according to the amount of 40µg siRNA per mouse: 40 µg of siRNA-a was dissolved in 100 µL of 5% glucose solution to obtain siRNA solution; Dissolve 6.8 μL of In vivo-jetPEI (Shanghai Noning Biotechnology Co., Ltd., in vivo-jetPEI Live DNA & si / miRNA Transfection Reagent, Cat. No.: 101000040) in 100 μL of 5% glucose solution to obtain In vivo-jetPEI solution; The In vivo-jetPEI solution was slowly added dropwise to the siRNA solution, gently pipetted to mix, and then allowed to stand at room temperature for 30 minutes to obtain the siRNA injection drug.

[0045] (3) Treatment The mice in the control and model groups were injected with 100 μL of 5% glucose solution, and the mice in the treatment group were injected with siRNA injection drugs twice a week for 4 consecutive weeks.

[0046] (4) Effect testing After the treatment, blood was collected from the mice in the control group, model group, and treatment group. After standing for 30 minutes, the blood was centrifuged at 3000 rpm for 10 minutes to separate the serum. TC (total cholesterol), TG (triglyceride), and LDL-C (low-density lipoprotein cholesterol) kits (Nanjing Jiancheng Biological) were used to detect the levels of various indicators in the serum of different treatment groups.

[0047] Mice were anesthetized and killed, and the aorta of the mice was isolated and ground in liquid nitrogen. TRIzol was added to lyse and extract RNA, and the expression of LncRNA-ENST00000564510.1 was detected according to the steps of Example 1; At the same time, the aortic tissue of the mice was sectioned and stained to evaluate the proportion of the positive staining area (Oil Red O positive area) to the total intima area of the blood vessels, and to calculate the proportion of atherosclerotic plaque area.

[0048] The expression level detection results of LncRNA-ENST00000564510.1 are as follows Figure 6 (a) Consistent with the results of the cell-based experiments, the expression level of LncRNA-ENST00000564510.1 in the aorta of a mouse model of atherosclerosis was significantly elevated, suggesting that this lncRNA may be involved in the pathogenesis of atherosclerosis. Further analysis showed that the expression level of LncRNA-ENST00000564510.1 in the aorta of mice treated with the siRNA injection drug described herein was significantly downregulated compared to the model group, demonstrating that the siRNA formulation can effectively target and inhibit the expression of the target lncRNA, demonstrating a positive intervention effect.

[0049] Changes in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) levels and plaque area ratios Figure 6As shown in (b), (c), (d), and (e), compared to the model group, mice treated with siRNA injection showed significant decreases in serum TC (58.53%), TG (53.98%), and LDL-C (56.99%) levels. This result demonstrates that the siRNA injection of the present invention not only effectively inhibits the abnormal expression of LncRNA-ENST00000564510.1 but also significantly improves lipid metabolism disorders induced by a high-fat diet, thereby demonstrating a significant therapeutic effect on atherosclerosis.

[0050] Histopathological analysis revealed a significant reduction in atherosclerotic plaque area in the aortas of mice treated with the siRNA injection (from 21.68% to 8.81%), with statistically significant differences compared to the model group. This result demonstrates that the siRNA injection provided by this invention can effectively inhibit the formation and progression of plaques and significantly improve atherosclerotic lesions induced by a high-fat diet.

Claims

1. A drug for treating atherosclerosis caused by a high-fat diet, characterized in that The drug consists of an inhibitor that targets and inhibits the expression of LncRNA-ENST00000564510.1 and a drug delivery carrier; The transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.

1.

2. The drug according to claim 1, characterized in that The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.

11.

3. The drug according to claim 2, characterized in that The concentration of the inhibitor in the drug is 200 μg / mL-1000 μg / mL.

4. The drug according to claim 3, characterized in that The drug delivery carrier is one of liposomes, polyethyleneimine and its derivatives, nanoparticles or cationic lipid complexes.

5. The drug according to claim 4, characterized in that The drug delivery carrier is polyethyleneimine and its derivatives.

6. Use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for treating atherosclerosis caused by a high-fat diet, characterized in that: The transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.

1.

7. The use according to claim 6, characterized in that The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.

11.

8. Use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for improving dyslipidemia caused by a high-fat diet, characterized in that: The transcript sequence of LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1; The inhibitor is a siRNA comprising a sense strand shown in SEQ ID NO.10 and an antisense strand shown in SEQ ID NO.11; The dyslipidemia is abnormally elevated total cholesterol, triglycerides and low-density lipoprotein cholesterol.

9. Use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for improving vascular endothelial cell damage caused by a high-fat diet, characterized in that: The transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1; The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.

11.

10. Use of an inhibitor targeting the expression of LncRNA-ENST00000564510.1 in the preparation of a drug for improving vascular inflammatory response induced by a high-fat diet, characterized in that: The transcript sequence of the LncRNA-ENST00000564510.1 is shown in SEQ ID NO.1; The inhibitor is siRNA comprising the sense strand shown in SEQ ID NO.10 and the antisense strand shown in SEQ ID NO.11.

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