Research ArticleAnalysis on the Expression and Prognostic Value of LncRNAFAF in Patients with Coronary Heart Disease

Hai Xu, Xiwen Zhang, Kun Yu, Gang Zhang, Yafei Shi, and Yicheng Jiang

Department of Cardiology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huai’an 223000, China

Correspondence should be addressed to Yicheng Jiang; jilei15506473690@163.com

Received 24 July 2020; Revised 4 September 2020; Accepted 25 September 2020; Published 3 November 2020

Academic Editor: Tao Huang

Copyright © 2020 Hai Xu et al. This is an open access article distributed under the Creative Commons Attribution License, whichpermits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Objective. To investigate the expression and prognostic value of LncRNA FAF in patients with coronary heart disease. Patients andMethods. 97 patients with coronary heart disease who came to our hospital were selected as the research group (RG), and 97 healthypeople who came to our hospital for physical examination during the same period were selected as the control group (CG).The serum LncRNA FAF, plasma homocysteine (HCY), lipoprotein A (Lp-a), serum tumor necrosis factor α (TNF-α), andhigh-sensitivity C-reactive protein (hsCRP) in the two groups of patients were detected, and their correlations wereanalyzed. Then, the predictive value and risk factors of FAF for poor prognosis of patients with coronary heart diseasewere analyzed. Results. The expression of LncRNA FAF in the serum of patients in the RG was significantly lower thanthat in the CG, and the expressions of HCY, Lp-a, TNF-α, and hsCRP were significantly higher than those in the CG(p<0.05). The AUC of FAF in the diagnosis of coronary heart disease was more than 0.9. FAF was negatively correlatedwith the coronary lesion vessels, HCY, Lp-a, TNF-α, and hsCRP expressions in patients with coronary heart disease(p < 0:05). The ROC of FAF for predicting poor prognosis in patients with coronary heart disease was greater than 0.9.Low expression of FAF; high expressions of HCY, Lp-a, and hsCRP; and increase of coronary lesion vessels wereindependent risk factors for poor prognosis in patients with coronary heart disease. Conclusions. LncRNA FAF was lowlyexpressed in the serum of patients with coronary heart disease, and it was of high value in the diagnosis and prediction ofpoor prognosis of coronary heart disease. It was also an independent risk factor for poor prognosis of patients withcoronary heart disease and may be a potential target for diagnosis and treatment of coronary heart disease.

1. Introduction

In recent years, with the changes of social environment andthe improvement of living standards, the incidence rate ofcardiovascular diseases is getting higher. Coronary heart dis-ease is one of the most common cardiovascular diseases, andacute myocardial infarction caused by coronary heart diseaseis also one of the main causes of disability or death in patientswith cardiovascular diseases, which poses a serious threat tohuman health [1, 2]. At present, coronary heart diseasepatients are mainly diagnosed and treated by cardiovascularintervention technology [3]. Although great progress hasbeen made in the diagnosis and treatment of coronary heartdisease with the development of medical technology, thereare still a large number of patients with coronary heart dis-ease who cannot be diagnosed and evaluated in time, result-

ing in patients who cannot be treated in time in suddensituations such as myocardial infarction [4, 5]. Therefore,how to timely and effectively diagnose and treat patients withcoronary heart disease is also one of the problems that needto be solved urgently in clinical practice.

In recent years, with the development of molecular biol-ogy, the application of molecular targeted diagnosis andtreatment technology in cardiovascular diseases is becom-ing more and more extensive, take long noncoding RNAANRIL, for example [6]. Long noncoding RNA (LncRNA)is a noncoding RNA with a length of more than 200 nt.In the past, LncRNA has been reported to play an impor-tant role in the occurrence of many diseases, including car-diovascular diseases [7]. For example, previous studies [8]found that LncRNA NEAT1 can inhibit vascular endothe-lial cell injury induced by oxidative stress by activating

HindawiBioMed Research InternationalVolume 2020, Article ID 9471329, 8 pageshttps://doi.org/10.1155/2020/9471329

miR-181d-5p/CDKN3 axis. LncRNA FAF is the latestLncRNA related to cardiovascular diseases [9]. Recentstudies [9] have suggested that it can inhibit apoptosis ofischemic and hypoxic myocardial cells together with theupregulation of fibroblast growth factor (FGF9), but itsclinical value in coronary heart disease has not been elabo-rated. FGF9 is a factor that has been proved to play animportant regulatory role in myocardial infarction, and itis believed to play an important regulatory role in coronaryartery vascular development [10], so we speculated whetherLncRNA FAF also plays an important role in the occur-rence of coronary heart disease. However, at present, nostudies were analyzed on the expression and clinical valueof LncRNA FAF in patients with coronary heart disease.

In order to carry out more analysis of LncRNA FAF onthe basis of previous scholars, we analyzed the expressionof LncRNA FAF in the serum of patients with coronary heartdisease and its value in the diagnosis and prognosis of coro-nary heart disease, so as to improve more clinical data forthe diagnosis and treatment of coronary heart disease.

2. Materials and Methods

From January 2016 to May 2018, 97 patients with coronaryheart disease who visited our hospital were selected as theRG, including 52 male and 45 female, with an average ageof (52:34 ± 6:48) years old. 97 healthy people who came toour hospital for physical examination during the same periodwere selected as the CG, including 54 male and 43 female,with an average age of (53:04 ± 6:52) years old. All patientsand their families agreed to participate in the experiment,which has been approved by the hospital ethics committee.(No. K(S)16-14).

The inclusion criteria are patients diagnosed as havingcoronary heart disease by coronary artery CT angiography.

The exclusion criteria are patients with serious blood sys-tem diseases; patients with other malignant tumor diseases;patients with severe immune system diseases; and patientswith severe liver and kidney dysfunction.

2.1. Detection of FAF Expression by qRT-PCR. 5mL of venousblood was taken from all subjects on an empty stomach andthen centrifuged at a temperature of 4°C for 10min at a speedof 1500 × g. After centrifugation, a supernatant was taken fordetection. TRIzol was added to the serum to extract totalRNA. The purity, concentration, and integrity of total RNAwere detected by a UV spectrophotometer and agarose gelelectrophoresis. cDNA reverse transcription was performedaccording to the kit instructions (TransGen Biotech, Beijing,China), and FAF detection was performed according to thekit instructions. The FAF amplification system was as fol-lows: cDNA 1μL, upstream and downstream primers each

0.4μL, 2X SYBR Green mixture 10μL, and Passive ReferenceDye (50X) 0.4μL. In the end, ddH2O was added to completeto 20μL. Amplification conditions were as follows: PCR reac-tion conditions: predegeneration at 95°C for 30 s, degenera-tion at 95°C for 5 s, anneal and extension at 60°C for 15 s,then followed by a total of 40 cycles. GAPDH was used asan internal parameter. Primer sequences are shown inTable 1. The experiment was repeated three times.

2.2. Detection of Other Related Indexes. We detected cardio-vascular disease-related factors and related inflammatory fac-tors in the serum of patients in the RG, including plasmahomocysteine (HCY), lipoprotein A (Lp-a), serum tumornecrosis factor α (TNF-α), and high-sensitivity C-reactiveprotein (hsCRP). PAF, ET-1 and TNF-α (Shanghai MeilianBiotechnology Co., Ltd.) were detected by ELISA. The oper-ation was strictly in accordance with the kit instructions.Immunofluorescence quantitative was used to detect theexpression of hsCRP (Boditech Med Inc.).

2.3. Statistical Methods. In this study, SPSS20.0 was used forstatistical analysis of experimental data. The counting datawere tested by the chi-squared test. The measurement datawere expressed as mean number ± standard deviation. t-testwas used for comparison between the two groups. The pairedt-test was used for the comparison before and after treat-ment. Pearson correlation was used for correlation analysis.Logistic regression model was used to analyze the risk factorsof adverse cardiovascular events. GraphPad Prism 6 was usedto draw the images in this experiment. There was a statisticaldifference with p < 0:05.

3. Results

3.1. Baseline Data. There was no significant difference in gen-der, age, and BMI between the two groups (p > 0:05), butthere was significant difference in the number of hyperten-sion (p < 0:05). More details are shown in Table 2.

3.2. Comparison of Serum FAF Expression between the TwoGroups of Subjects. The FAF expression of patients in theRG was 0:63 ± 0:12, significantly lower than that in the CG(0:91 ± 0:15), and the difference was statistically significant(p < 0:05). We analyzed the FAF in patients in the RG,and the results indicated that the expression of serumFAF in patients with multivessel coronary artery disease(0:45 ± 0:08) was significantly lower than that in patientswith double-vessel (0:61 ± 0:08) and single-vessel disease(0:73 ± 0:08), and the expression of serum FAF in patientswith double-vessel disease was significantly lower than thatin patients with single-vessel disease, and the differenceswere statistically significant (p < 0:05). More details areshown in Figure 1.

Table 1: Primer sequence.

Factors Upstream primers Downstream primers

FAF 5′-CGCTAAAGGCACAGGGTCAG-3′ 5′-CACCAACCTTTCCCTTCCAGTC-3′GAPDH 5′-GGCACAGTCAAGGCTGAGAATG-3′ 5′-ATGGTGGTGAAGACGCCAGTA-3′

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3.3. Expression of HCY, Lp-a, TNF-α, and hsCRP in Serum ofSubjects in the Two Groups. The expressions of HCY(24:42 ± 5:31) umol/L, Lp-a (214:15 ± 26:47) mmol/L, TNF-α

(66:27 ± 7:31) pg/mL, and hsCRP (8:49 ± 1:31) mg/L in theRG of patients were significantly higher than those of HCY(8:26 ± 1:67) umol/L, Lp-a (91:33 ± 14:62) mmol/L, TNF-α

Table 2: Baseline data.

FactorsRG CG

t/χ2 pn = 97 n = 97

Gender 0.083 0.773

Male 52 (53.61) 54 (55.67)

Female 45 (46.39) 43 (44.33)

Age/years old 52:34 ± 6:48 53:04 ± 6:52 0.750 0.454

BMI (kg/m2) 23:54 ± 2:16 23:66 ± 2:21 0.382 0.703

Types — —

Myocardial infarction 42 (43.30) —

Nonmyocardial infarction 55 (56.70) —

Count of coronary artery stenosis — —

Single vessel 31 (31.96) —

Double vessel 35 (36.08) —

Multiple vessels 32 (32.99) —

Drinking history 0.083 0.774

Yes 52 (53.61) 50 (51.55)

No 45 (46.39) 47 (48.45)

Smoking history 0.021 0.885

Yes 43 (44.33) 44 (45.36)

No 54 (55.67) 53 (54.64)

Hypertension 8.269 0.004

Yes 61 (62.89) 41 (42.27)

No 36 (37.11) 56 (57.73)

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Figure 1: Comparison of serum FAF expression between the two groups of subjects. (a) The expression of FAF in the RG was significantlylower than that in the CG. (b) The expression of serum FAF in patients with multivessel coronary artery disease was significantly lower thanthat in patients with double-vessel and single-vessel disease, and the expression of serum FAF in patients with double-vessel disease wassignificantly lower than that in patients with single-vessel disease. ∗ indicates p < 0:05.

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(32:16 ± 2:84) pg/mL, and hsCRP (4:02 ± 0:83) mg/L in theCG. The difference was statistically significant (p < 0:05). Moredetails are shown in Figure 2.

3.4. Diagnostic Value and Correlation Analysis of FAF forCoronary Heart Disease. ROC curve analysis indicated thatthe AUC of FAF in the diagnosis of coronary heart diseasewas 0.935, which had a high diagnostic value. Moreover,there was a negative correlation between FAF and coronarylesion vessels and the expression of HCY, Lp-a, TNF-α, andhsCRP in serum of patients with coronary heart disease(p < 0:05). More details are shown in Figure 3.

3.5. The Predictive Value of FAF for Poor Prognosis inPatients with Coronary Heart Disease. All patients withcoronary heart disease were followed up for one year.Patients were divided into a MACE group (40 cases)and non-MACE group (57 cases) according to the occur-rence of adverse cardiac events (MACE) during thefollow-up period. After comparing the serum FAF inthe two groups of patients, it was found that the serum

FAF of patients in the MACE group was significantlylower than that in the non-MACE group (p < 0:05).ROC analysis indicated that the AUC of FAF for predict-ing poor prognosis of patients with coronary heart dis-ease was 0.916, which had high predictive value. Moredetails are shown in Figure 4.

3.6. Univariate Analysis of Poor Prognosis in Patients withCoronary Heart Disease. After univariate analysis of patientsin the MACE group and non-MACE group, it was found thatthere were no significant differences in gender, age, drinking,and other aspects between the two groups (p > 0:05), andthere were significant differences in FAF, HCY, Lp-a, hsCRP,and lesion vessels (p < 0:05). More details are shown inTable 3.

3.7. Multivariate Analysis of Poor Prognosis in Patients withCoronary Heart Disease. We included FAF, HCY, Lp-a,hsCRP, and lesion vessels for analysis and listed them asdependent variables for assignment (Table 4). MACE ornot was taken as the dependent variable. The logistic

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Figure 2: Expression of HCY, Lp-a, TNF-α, and hsCRP in serum of subjects in the two groups. (a) HCY expression in the RG wassignificantly higher than that in the CG. (b) Lp-a expression in the RG was significantly higher than that in the CG. (c) TNF-α expressionin the RG was significantly higher than that in the CG. (d) hsCRP expression in the RG was significantly higher than that in the CG.∗ indicates p < 0:05.

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regression model was used for multivariate analysis. Theresults indicated that FAF, HCY, Lp-a, hsCRP, and lesionvessels were independent risk factors for poor prognosis ofcoronary heart disease patients (Table 5).

4. Discussion

In recent years, with the development of sequencing technol-ogy, LncRNA has also been discussed as a key research

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Figure 3: Diagnostic value and correlation analysis of FAF for coronary heart disease. (a) ROC analysis of FAF in the diagnosis of coronaryheart disease. (b) There was a negative correlation between FAF and coronary lesion vessels in patients with coronary heart disease(r = −0:881, p < 0:001). (c) The FAF and PAF expressions were negatively correlated (r = −0:728, p < 0:001). (d) FAF and ET-1 expressionswere negatively correlated (r = 0 − 704, p < 0:001). (e) FAF and TNF-α expressions were negatively correlated (r = −0:674, p < 0:05).(f) FAF and hsCRP expressions were negatively correlated (r = −0:664, p < 0:05).

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Figure 4: The predictive value of FAF for poor prognosis of patients with coronary heart disease: (a) low expression of FAF in serum ofpatients with poor prognosis of coronary heart disease; (b) the predictive value of FAF for poor prognosis of patients with coronary heartdisease. ∗ indicates p < 0:05.

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direction in the research of cardiovascular diseases. Manymechanisms of LncRNA in diseases have been extensivelystudied and elaborated [11, 12]. Coronary artery disease isone of the major types of cardiovascular diseases. Due tothe limited treatment methods and the side effects causedby long-term drug use, there are still great challenges in theearly diagnosis and treatment of coronary heart disease[13, 14]. LncRNA is a potential diagnosis and treatmenttarget for coronary heart disease in the future, and there

are also many related researches. For example, previous stud-ies [15] indicated that the specificity of plasma LncRNAmarker for diagnosis of coronary heart disease can reachmore than 90%.

This study was designed to discuss the expression ofLncRNA FAF in the serum of patients with coronary heartdisease and its related clinical significance. FAF belongs toLncRNA which is found to be abnormally expressed in car-diovascular diseases. In the past, many researches have beenconducted on the mechanism of LncRNA in coronary arterydiseases. For example, research [16] concluded that LncRNAHOTTIP can promote the proliferation andmigration of vas-cular endothelial cells by activating the Wnt/β-catenin path-way. Other studies [17] have found that the level of LncRNAH19 in plasma was related to the risk of coronary artery dis-ease. However, there are few related studies on FAF. Previousstudies [9] claimed that LncRNA FAF and FGF9 were locatedon the same chromosome and can be combined by reversecomplementation. In our study, we first found that FAFwas low expressed in the serum of patients with coronaryheart disease and found that it had high value in the diagnosisof coronary heart disease and the prediction of poor progno-sis of coronary heart disease. In the past research [18], it wassaid that FGF9 can improve the systolic function of the heartby reducing interstitial fibrosis, thus reducing the mortalityrate of heart failure. A study [19] pointed out that LncRNAFAF can inhibit cardiac fibrosis by targeting FGF9. In thisstudy, it was found that FAF was lowly expressed in theprocess of myocardial fibrosis, which is similar to ourconclusion.

Then, in order to further analyze the relationshipbetween FAF and coronary heart disease, we first detectedthe expressions of HCY, Lp-a, TNF-α, and hsCRP in theserum of patients with coronary heart disease. The resultsindicated that the expressions of HCY, Lp-a, TNF-α, andhsCRP in the serum of patients with coronary heart disease

Table 3: Univariate analysis of poor prognosis in patients with coronary heart disease.

FactorsMACE group Non-MACE group

t/χ2 pn = 40 n = 57

Gender (n (%)) 0.053 0.818

Male 22 (55.00) 30 (52.63)

Female 18 (45.00) 27 (47.37)

Age/years old 52:26 ± 6:35 52:44 ± 6:51 0.135 0.893

BMI (kg/m2) 23:49 ± 2:22 23:58 ± 2:18 0.199 0.843

Lesion vessels 7.406 0.025

Single vessel 10 (25.00) 21 (36.84)

Double vessel 11 (27.50) 26 (45.61)

Multiple vessels 19 (47.50) 13 (22.81)

FAF 0:43 ± 0:09 0:71 ± 0:13 11.78 <0.001HCY (μmol/L) 26:31 ± 4:26 20:09 ± 3:81 7.537 <0.001Lp-a (mmol/L) 228:45 ± 18:31 202:66 ± 15:73 7.426 <0.001TNF-α (pg/mL) 67:26 ± 7:02 66:05 ± 7:11 0.829 0.409

hsCRP (mg/L) 9:63 ± 1:02 7:83 ± 1:06 8.361 <0.001

Table 4: Assignment table.

Factors Assignment

Lesion vessels Single vessel, double vessel = 1, multiple vessels = 2

FAFData belonged to continuous variables and was

analyzed with original data

HCYData belonged to continuous variables and was

analyzed with original data

Lp-aData belonged to continuous variables and was

analyzed with original data

hsCRPData belonged to continuous variables and was

analyzed with original data

Table 5: Multivariate analysis of poor prognosis in patients withcoronary heart disease.

Factor β S.E Wald OR 95% CI p

Lesion vessels 0.459 0.211 4.662 1.631 1.042-2.419 0.028

FAF 0.919 0.187 25.073 2.521 1.751-3.611 <0.001HCY 0.437 0.141 9.154 1.537 1.169-2.029 0.002

Lp-a 1.085 0.467 5.273 2.991 1.176-7.521 0.023

hsCRP 0.982 0.368 7.009 2.693 1.288-5.563 0.007

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were significantly higher than those in the CG. HCY is a sul-fur amino acid in the metabolic process of human cells, andits content is generally lower in the human body [20]. Previ-ous studies [21] pointed out that the higher the level of HCY,the greater the risk of cardiovascular diseases. Lp-a, as a pro-tein complex synthesized in the liver, can prevent blood clotdissolution in blood by combining with fibrin, which is themain cause of atherosclerosis [22]. TNF-α and hsCRP bothbelong to inflammatory factors. In coronary heart disease,hsCRP is more representative as one of inflammatorymarkers, which can directly induce monocytes to aggregateinto atherosclerotic plaques, thus causing vascular endothe-lial dysfunction [23]. The increase of the serum hsCRP levelin patients with coronary heart disease often represents themore serious myocardial injury in patients [24]. Throughcorrelation analysis, we found that FAF was negatively corre-lated with the expressions of HCY, Lp-a, TNF-α, and hsCRPin the serum of patients with coronary heart disease, whichindicated that FAF may be closely related to the formationof coronary heart disease and myocardial injury, but the spe-cific regulatory relationship between FAF and myocardialinjury is still unclear. In the past, there are relatively manystudies on other LncRNA in coronary heart disease. Forexample, LncRNA-LET can reduce hypoxia-induced myo-cardial cell damage by regulating miR-138 [25]. There arealso studies [26] that pointed out that LncRNA BANCRmay be used as a biomarker for the screening and preventionof coronary heart disease. However, the research on FAF incoronary heart disease is still at a relatively blank stage. Then,in order to further enrich our data, we analyzed the risk fac-tors for poor prognosis of patients with coronary heart dis-ease by logistic multiple regression. The results indicatedthat low expression of FAF and high expression of HCY,Lp-a, hsCRP, and multivessel coronary artery disease wereindependent risk factors for poor prognosis of patients withcoronary heart disease. In the past, previous studies clearlypointed out that elevated HCY, Lp-a, and hsCRP were inde-pendent risk factors for coronary heart disease [27, 28],which is similar to our conclusion. The increase of coronarylesion vessels also represented that the patient’s conditionwas more serious, which may also be one of the causes forthe occurrence of MACE in patients [29]. However, this isthe first time that we have found that the low expression ofFAF is an independent risk factor for poor prognosis ofpatients with coronary heart disease, but more studies areneeded to prove it in the future.

There are still some deficiencies in this study. For exam-ple, we have not explored the role of FAF in coronary heartdisease from basic experiments. Secondly, due to the lack ofrelevant studies, a large number of experiments are stillneeded to demonstrate our research.

5. Conclusions

To sum up, LncRNA FAF was lowly expressed in the serumof patients with coronary heart disease, and it was of highvalue in the diagnosis and prediction of poor prognosis ofcoronary heart disease. It was also an independent risk factorfor poor prognosis of patients with coronary heart disease

and may be a potential target for the diagnosis and treatmentof coronary heart disease.

Data Availability

The data can be unconditionally disclosed.

Conflicts of Interest

The authors declare that they have no conflict of interest.

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