miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are sensitive biomarkers to diagnose sudden cardiac death

Abstract Background Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. Methods This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Results It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71–97.06% and specificity of 70–100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407–0.8667). Conclusion miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

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miR-3113-5p, miR-223-3p, miR-133a-3p, and miR-499a-5p are Sensitive Biomarkers to Diagnose Sudden Cardiac Death

10.21203/rs.3.rs-147657/v1 ◽

2021 ◽

Author(s):

Fengping Yan ◽

Yuanyuan Chen ◽

Xing Ye ◽

Fu Zhang ◽

Shiquan Wang ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Cardiac Death ◽

Quantitative Polymerase Chain Reaction ◽

Control Group ◽

Pathological Changes ◽

Diagnostic Challenge ◽

Roc Curve Analysis ◽

Injury Death ◽

Diagnostic Biomarkers ◽

Autopsy Findings

Abstract BackgroundSudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. MethodsThis study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as acute myocardial infarction (AMI) without positive autopsy findings and 16 as atherosclerotic cardiovascular diseases (ASCVD) with gross myocardial scar. Carbon monoxide (CO) intoxication (n=14) and fatal injury death (n=14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Resultsit showed that heart samples from the AMI group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, ROC curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71-97.06% and specificity of 70-100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the AMI heart as relative to ASCVD, and a combination of two miRNAs presented higher diagnostic value (AUC=0.7407-0.8667). ConclusionmiR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

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Diagnostic Application of Postmortem Cardiac Troponin I Pericardial Fluid/Serum Ratio in Sudden Cardiac Death

Diagnostics ◽

10.3390/diagnostics11040614 ◽

2021 ◽

Vol 11 (4) ◽

pp. 614

Author(s):

Diana Hernández-Romero ◽

María del Rocío Valverde-Vázquez ◽

Juan Pedro Hernández del Rincón ◽

José A. Noguera-Velasco ◽

María D. Pérez-Cárceles ◽

...

Keyword(s):

Myocardial Infarction ◽

Sudden Cardiac Death ◽

Cardiac Troponin ◽

Cardiac Death ◽

Troponin I ◽

Sampling Site ◽

Pericardial Fluid ◽

Cardiac Troponin I ◽

Control Group ◽

Complementary Method

In approximately 5% of unexpected deaths, establishing a conclusive diagnosis exclusively on the basis of anatomo-pathological findings in a classic autopsy is difficult. Postmortem biomarkers have been actively investigated as complementary indicators to help to reach valid conclusions about the circumstances of death. Several studies propose either the pericardial fluid or peripheral veins as a location for troponin determination, but the optimum sampling site is still a matter of debate. Our objective was to evaluate the association between the ratio of troponin values in the pericardial fluid and serum (determined postmortem) and the diagnosis of acute myocardial infarction (AMI) in the context of sudden cardiac death. We included 175 forensic cases. Two groups were established: AMI deaths (48; 27.4%) and the control group (127; 72.6%). The cardiac Troponin I (cTnI) values in the pericardial fluid and the troponin ratio were found to be associated with the cause of death. Univariate regression analyses showed that both age and the cTnI ratio were significantly associated with the diagnosis of AMI death. In a multivariate analysis, adjusting for confounding factors, the age and cTnI ratio were independent predictors of death from myocardial infarction. We performed a receiver operating characteristic (ROC) curve for the cTnI ratio for AMI death and selected a cut-off point. Our biomarker was found to be a valuable and highly effective tool for use in the forensic field as a complementary method to facilitate diagnosis in nonconclusive autopsies.

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How to Predict the Impact of Methylphenidate on Cardiovascular Risk in Children with Attention Deficit Disorder: Methylphenidate Improves Autonomic Dysfunction in Children with ADHD

ISRN Pharmacology ◽

10.5402/2012/170935 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 7

Author(s):

Reiner Buchhorn ◽

Christian Müller ◽

Christian Willaschek ◽

Kambiz Norozi

Keyword(s):

Sudden Cardiac Death ◽

Attention Deficit ◽

Attention Deficit Disorder ◽

Cardiac Death ◽

Control Group ◽

Healthy Children ◽

Children With Adhd ◽

Heart Defect ◽

Adhd Children ◽

The Impact

Background. Although stimulants have long been touted as treatments for attention deficit disorder with or without hyperactivity (ADHD), in recent years, increasing concerns have been raised about the cardiovascular safety of these medications. We aimed to prove if measurements of autonomic function with time domain analysis of heart rate variability (HRV) in 24-hour Holter ECG are useful to predict the risk of sudden cardiac death in ADHD children and adolescents. Methods. We analysed HRV obtained from children with the diagnosis of ADHD prior to (N=12) or during medical therapy (N=19) with methylphenidate (MPH), aged 10.8±2.0 years (mean ± SD), who were referred to our outpatient Paediatric Cardiology Clinic to rule out heart defect. As a control group, we compared the HRV data of 19 age-matched healthy children without heart defect. Results. Average HRV parameters from 24-hour ECG in the ADHD children prior to MPH showed significant lower values compared to healthy children with respect to rMSSD (26±4 ms versus 44±10 ms, P≤0.0001) and pNN50 (6.5±2.7% versus 21.5±9.0%, P≤0.0001). These values improved in MPH-treated children with ADHD (RMSSD: 36±8 ms; pNN50: 14.2±6.9%). Conclusion. Children who suffer from ADHD show significant changes in HRV that predominantly reflects diminished vagal tone, a well-known risk factor of sudden cardiac death in adults. In our pilot study, MPH treatment improved HRV.

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Early repolarisation among athletes

BMJ Open Sport & Exercise Medicine ◽

10.1136/bmjsem-2019-000694 ◽

2020 ◽

Vol 6 (1) ◽

pp. e000694

Author(s):

Femke M A P Claessen ◽

Heidi A P Peeters ◽

Bastiaan J Sorgdrager ◽

Peter L J van Veldhoven

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Sudden Cardiac Death ◽

Ventricular Fibrillation ◽

Outpatient Clinic ◽

Cardiac Death ◽

Multivariable Analysis ◽

Control Group ◽

Multivariable Logistic Regression Analysis ◽

Athlete Group

ObjectivesTraditionally, early repolarisation (ER) is considered a benign ECG variant, predominantly found in youths and athletes. However, a limited number of studies have reported an association between ER and the incidental occurrence of ventricular fibrillation or sudden cardiac death. Yet definite, direct comparisons of the incidence of ER in unselected, contemporary populations in athletes as compared with non-athletes and across different sports are lacking. This study therefore aimed to investigate whether ER is more common among athletes as compared with non-athletes, and if ER patterns differ between sport disciplines based on static and dynamic intensity.MethodsTo assess ER we retrospectively analysed ECGs of 2241 adult subjects (2090 athletes, 151 non-athletes), who had a sports medical screening between 2010 and 2014 in an outpatient clinic. The outcome was tested for confounders in a multivariable logistic regression analysis.ResultsER was found in 502 athletes (24%). We found a 50% higher prevalence of ER in the athlete group compared with the control group (OR 1.5 (SE 0.34), adjusted 95% CI 1.0 to 2.4) in multivariable analysis. A 30% higher prevalence of ER in the inferior leads only (OR 1.3 (SE 0.38), adjusted 95% CI 0.74 to 2.3), a 120% higher prevalence of ER in the lateral leads only (OR 2.2 (SE 1.0), adjusted 95% CI 0.87 to 5.4), and a 20% higher prevalence of ER in the inferior and lateral leads (OR 1.2 (SE 0.49), adjusted 95% CI 0.55 to 2.7) was found in athletes.ConclusionAthletes had a 50% higher prevalence of ER and a 30% higher prevalence of ER in the inferior leads specifically. There was no association between training duration or sports discipline and ER.

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Expression of the Novel Cardiac Biomarkers sST2, GDF-15, suPAR, and H-FABP in HFpEF Patients Compared to ICM, DCM, and Controls

Journal of Clinical Medicine ◽

10.3390/jcm9041130 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1130

Author(s):

Peter Jirak ◽

Rudin Pistulli ◽

Michael Lichtenauer ◽

Bernhard Wernly ◽

Vera Paar ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Biomarkers ◽

Control Group ◽

The Novel ◽

Significant Elevation ◽

Serum Samples ◽

Diagnostic Challenge ◽

Diagnostic Biomarkers ◽

Diagnostic Potential ◽

Cardiovascular Biomarkers

Background: Heart failure with preserved ejection fraction (HFpEF) remains an ongoing therapeutic and diagnostic challenge to date. In this study we aimed for an analysis of the diagnostic potential of four novel cardiovascular biomarkers, GDF-15, H-FABP, sST2, and suPAR in HFpEF patients compared to controls as well as ICM, and DCM. Methods: In total, we included 252 stable outpatients and controls (77 DCM, 62 ICM, 18 HFpEF, and 95 controls) in the present study. All patients were in a non-decompensated state and on a stable treatment regimen. Serum samples were obtained and analyzed for GDF-15 (inflammation, remodeling), H-FABP (ischemia and subclinical ischemia), sST2 (inflammation, remodeling) and suPAR (inflammation, remodeling) by means of ELISA. Results: A significant elevation of GDF-15 was found for all heart failure entities compared to controls (p < 0.005). Similarly, H-FABP evidenced a significant elevation in all heart failure entities compared to the control group (p < 0.0001). Levels of sST2 were significantly elevated in ICM and DCM patients compared to the control group and HFpEF patients (p < 0.0001). Regarding suPAR, a significant elevation in ICM and DCM patients compared to the control group (p < 0.0001) and HFpEF patients (p < 0.01) was observed. An AUC analysis identified H-FABP (0.792, 95% CI 0.713–0.870) and GDF-15 (0.787, 95% CI 0.696–0.878) as paramount diagnostic biomarkers for HFpEF patients. Conclusion: Based on their differences in secretion patterns, novel cardiovascular biomarkers might represent a promising diagnostic tool for HFpEF in the future.

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Implantable cardioverter defibrillator - powerful weapon in primary and secondary prevention of sudden cardiac death

Vojnosanitetski pregled ◽

10.2298/vsp171003010k ◽

2019 ◽

Vol 76 (10) ◽

pp. 1007-1013

Author(s):

Tomislav Kostic ◽

Dragana Stanojevic ◽

Ognjen Gudelj ◽

Dragan Milic ◽

Svetozar Putnik ◽

...

Keyword(s):

Drug Therapy ◽

Sudden Cardiac Death ◽

Medical Therapy ◽

Cardiac Death ◽

Left Ventricular ◽

Cardiac Insufficiency ◽

Cardiac Resynchronization ◽

Left Ventricular Ejection ◽

Control Group ◽

Ventricular Ejection Fraction

Bacgraund/Aim. Sudden cardiac death (SCD) is one of the biggest problems of the contemporary medicine. Large studies showed that anti-arrhythmics, including amiodarone, are not effective in prevention of SCD in the patients with cardiac diseases who were on drug treatment. Those patients who received implantable cardioverter defibrillators (ICD) had better survival. The aim of this paper was to determine whether the patients receiving the ICD in the primary and secondary SCD prevention have longer survival than the patients treated exclusively with drug therapy. Methods. We included 1,260 patients with cardiac insufficiency and reduced left ventricular ejection fraction (LVEF < 35%) who were at high risk for malignant ventricular arrhythmias and SCD. Five hundred forty patients received ICD therapy. The cardiac resynchronization therapy ? CRT/ICD group (n = 270) comprised the patients with cardiac insufficiency and CRT/ICD pacemaker at an optimal medical therapy. In the control group (n = 450), there were the patients with cardiac insufficiency (NYHA functional class 3?4, LVEF ? 35%, QRS duration ? 130 ms), at optimum drug therapy. Results. In the ICD group, there was a statistically significant increase in end-systolic volume (ESV) from 92.68 mL to 99.05 mL. In the group of patients with cardiac insufficiency who were on drug therapy, there was a significant decrease in LVEF (33.15% vs. 30.2%; p = 0.017), 6-minute walk distance (6 MWT distance) (216.55 m vs. 203.27 m, p = 0.003). In the same group, there was an increase in the values of ESV (90.19 mL vs. 95.41 mL; p = 0.011). An increase in the mortality rate in the group of patients with drug therapy compared to the CRT/ICD and ICD groups was statistically significant (p < 0.05). Conclusions. An ICD pacemaker implantation significantly reduces mortality compared to medical therapy only. In addition, the patients who have CRT in addition to ICD pacemaker, have a significantly better quality of life and increase in LVEF.

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Association of isolated T inversion and sudden cardiac death – etiology and gender differences

European Heart Journal ◽

10.1093/ehjci/ehaa946.2903 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

M.A.E Haukilahti ◽

L Holmstrom ◽

J Vahatalo ◽

T.V Kentta ◽

L Pakanen ◽

...

Keyword(s):

Gender Differences ◽

Sudden Cardiac Death ◽

General Population ◽

Cardiac Death ◽

Left Ventricular ◽

Common Finding ◽

Control Group ◽

Funding Source ◽

Increased Risk ◽

Significant Difference

Abstract Background Inferolateral T wave inversion has been associated with increased risk of mortality and sudden cardiac death (SCD) in general population. However, the association between isolated T inversion and SCD is still unclear. Purpose The purpose of this study was to examine whether isolated T inversion associates with SCD, and find out possible gender differences. Methods FinGesture Study has systematically collected clinical data and medico-legal autopsy data from 5,869 consecutive SCD victims (mean age 64.9±12.4 yrs.) in Northern of Finland between years 1998 and 2017. Previously recorded electrocardiograms (ECG) were available and analyzed in 1,101 subjects. The control group consisted of 7,217 subjects representative of Finnish general population (mean age 51.5±12.4 yrs.). T inversion was interpreted isolated if there was at least two T inversions ≥−0.1 mV in at least two contiguous leads, and there were no ECG signs of left ventricular hypertrophy (LVH) defined by Sokolow-Lyon criteria or bunchle brand block (BBB) attached to it. Results In a current study, isolated T inversion was more common finding among SCD victims compared to general population: isolated T inversion in any leads 10.9% vs. 0.9% (SCD vs. general population, p<0.001), laterally 7.7% vs. 0.1% (p<0.001), inferiorly 3.2% vs. 0.5% (p<0.001) and anteriorly 2.9% vs. 0.4% (p<0.001). Particularly, isolated T inversion seemed to assoaciate with ischemic SCD taking into account that 61.5% of the total isolated T inversions were seen in ischemic SCD victims (p=0.018). In addition, 62.1% of the inferior isolated T inversions (p=0.023) and 61.7% of the lateral isolated T inversions (p=0.031) were in ischemic SCD victims versus 37.9% and 38.3% in non-ischemic SCD victims, respectively. The prevalence of isolated T inversion in any lead was also higher among male SCD victims compared to female victims (12.8% vs. 8.2%, p<0.001, respectively). There was no statistically significant difference in the prevalence of LVH and strain changes between the populations. Among bundle branch blocks left BBB was predictably more typical in SCD victims (5.8% vs. 0.5%, p<0.001). Conclusion We noticed an association between isolated T inversion and SCD. The association was most prominent in males and in those with ischemic etiology of SCD. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): The Finnish Medical Foundation, Finnish Foundation for Cardiovascular Research

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A study of new molecular genetic markers of sudden cardiac death identified in the analysis of the results of whole-exome sequencing

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.05.33-35 ◽

2020 ◽

pp. 33-35

Author(s):

А.А. Иванова ◽

Е.С. Мельникова ◽

А.А. Гуражева ◽

С.К. Малютина ◽

В.П. Новоселов ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Genetic Markers ◽

Cardiac Death ◽

Molecular Genetic ◽

Control Group ◽

Nucleotide Polymorphisms ◽

Molecular Genetic Markers ◽

Whole Exome

Целью исследования является подтверждение ассоциации с внезапной сердечной смертью однонуклеотидных полиморфизмов rs77270326, rs34643859, выявленных в ходе собственного полноэкзомного секвенирования как возможных молекулярно-генетических маркеров внезапной сердечной смерти. В группе внезапной сердечной смерти (n=400, средний возраст умерших 53,2±8,7 года, доля мужчин - 70,9%, женщин - 29,1%) и контрольной группе (n=400, средний возраст 53,1±8,3 года, мужчины - 68,3 %, женщины - 31,7%) проведено генотипирование по выбранным полиморфизмам методом ПЦР-ПДРФ по авторским протоколам. По частотам генотипов и аллелей полиморфизма rs77270326 не найдено статистически значимых различий между группами (p>0,05). В группе женщин в возрасте до 50 лет выявлено статистически значимое уменьшение доли носительниц генотипа ТТ в группе внезапной сердечной смерти (32,3%) по сравнению с контрольной группой (60,0%) (ОШ=0,32, 95%ДИ 0,11-0,91, р=0,04). Таким образом, однонуклеотидный полиморфизм rs77270326 не ассоциирован с внезапной сердечной смертью. Для женщин младше 50 лет генотип ТТ полиморфизма rs34643859 ассоциирован с протективным эффектом в отношении внезапной сердечной смерти. The aim of the study is to confirm the association with sudden cardiac death of single-nucleotide polymorphisms rs77270326, rs34643859, identified during own whole-exome sequencing as possible molecular genetic markers of sudden cardiac death. In the group of sudden cardiac death (n = 400, the average age of the dead - 53.2 ± 8.7 years, the proportion of men - 70.9%, women - 29.1%) and the control group (n = 400, average age - 53 , 1 ± 8.3 years, men - 68.3%, women - 31.7%) genotyping of the selected polymorphisms was conducted by PCR-RFLP method according to the authors’ protocols. According to the frequencies of genotypes and alleles of rs77270326 polymorphism, no statistically significant differences were found between the groups (p>0.05). A group of women under the age of 50 revealed a statistically significant decrease in the proportion of carriers of the TT genotype in the group of sudden cardiac death (32.3%) compared with the control group (60.0%) (OR = 0.32, 95% CI 0, 11-0.91, p = 0.04). Thus, the rs77270326 is not associated with sudden cardiac death. For women under the age of 50, the TT genotype of rs34643859 polymorphism is associated with a protective effect against sudden cardiac death.

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424 - Cardiac Healthcare Disparities in Schizophrenia at the End-of-Life

International Psychogeriatrics ◽

10.1017/s1041610221001836 ◽

2021 ◽

Vol 33 (S1) ◽

pp. 45-46

Author(s):

Baruth J. ◽

Bateman D. ◽

Bateman P. ◽

Kovacs R. ◽

Lapid M.

Keyword(s):

Cardiovascular Disease ◽

Sudden Cardiac Death ◽

End Of Life ◽

Healthcare Utilization ◽

Cardiac Death ◽

Healthcare Disparities ◽

Density Lipoprotein ◽

Control Group ◽

Qtc Interval ◽

To Receive

Background:Schizophrenia is a serious mental illness associated an early mortality of 15 to 20 years. Eighty percent of deaths are due to cardiovascular disease, and the risk of sudden cardiac death is three- times greater than the general population. Both modifiable and non-modifiable risk factors like lifestyle, medication side-effects, genetics, and healthcare disparities have been identified, but this relationship is not fully understood.Research Objective:To examine cardiac-related healthcare utilization of individuals with schizophrenia at the end-of-life.Method:As a retrospective cohort study the Mayo Clinic Unified Data Platform (UDP) was used to identify a schizophrenia group (SG) (n = 610) 50 years or older with a death date between 1/1/1999 – 1/1/2019 and control group (n = 610) matched by gender (53% women) and age of death (72.8 ± 12.4 years). Measures of cardiovascular healthcare utilization were evaluated within a 12-month period prior to death. Pearson’s chi-square (χ2), analysis of variance was used (ANOVA), and logistic regression were used for statistical analysis.Results:SG was more likely than controls to be unmarried, unemployed, or from racial minority groups (all p<0.001) and was more likely to have diabetes mellitus (p<0.001) or cardiovascular disease (p=0.004). SG was less likely to receive an electrocardiogram (ECG) (p<0.001), echocardiogram (p=0.003), or cardiac catheterization procedure (p<0.001), and more likely to receive hemoglobin A1C testing (p<0.001). Of those receiving an ECG, SG had a greater mean QTc interval (453.8 ms vs. 438.0 ms; p<0.001) and were twice as likely to have an ECG result interpreted as “prolonged QTc” (p<0.001).Between group differences for utilization of troponin or low-density lipoprotein testing, or pacemaker- related procedures were not statistically significant.Conclusion:Individuals with schizophrenia in this cohort were less likely to receive cardiovascular evaluations and interventions during their last year of life. Despite the higher likelihood for prolonged QTc, a recognized biomarker of cardiac risk, SG was less likely to receive an ECG. Given the greater cardiac comorbidity and higher risk of sudden cardiac death in schizophrenia, interventions are needed to address these disparities in care.

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Evaluation of Plasma MMP-9 and VEGF-A mRNAs as Non-invasive Diagnostic Biomarkers in Women with Endometriosis

Gene Cell and Tissue ◽

10.5812/gct.118656 ◽

2021 ◽

Vol In Press (In Press) ◽

Author(s):

Sepideh Abdollahi ◽

Pantea Izadi ◽

Shahla Noori Ardebili ◽

Samaneh Chegeni ◽

Mir Saead Yekaninejad

Keyword(s):

Plasma Level ◽

Quantitative Polymerase Chain Reaction ◽

Mrna Level ◽

Control Group ◽

P Value ◽

Mrna Levels ◽

Diagnostic Biomarker ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Significant Difference

Background: Endometriosis is one of the common gynecological diseases and can lead to pelvic pain, dysmenorrhea, dyspareunia, and infertility in women. Thus, accurate and early diagnosis is a pivotal issue and an essential need for managing this disorder. At the present, the gold standard diagnostic method for endometriosis is laparoscopic surgery that is an invasive method and can lead to delay in diagnosis. Thus, there is an immediate necessity to search for non-invasive diagnostic biomarkers, such as blood-based ones. Objectives: Matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor-A (VEGF-A) have essential roles in the pathogenesis of endometriosis. Therefore, in this study, we evaluated the plasma mRNA levels of MMP-9 and VEGF-A, as potential non-invasive diagnostic biomarkers for endometriosis. Methods: This study included 48 women (24 cases and 24 controls) who underwent laparoscopy for suspected endometriosis. Preoperative plasma samples were collected, and after RNA extraction, the levels of MMP-9 and VEGF-A mRNAs were determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: Plasma MMP-9 mRNA level was statistically higher in endometriosis patients compared with the control group (P value = 0.01). However, plasma VEGF-A mRNA level did not show a significant difference between the two groups (P value =0.5). Conclusions: It seems that the plasma level of MMP-9 mRNA in endometriosis patients is significantly higher than in non-endometriosis women. This finding can provide new insights regarding this mRNA’s applicability as a non-invasive diagnostic biomarker for discovering new cases of endometriosis (newly diagnosed). According to our results, despite the suggested role of VEGF-A in endometriosis pathogenesis, it seems that the plasma level of VEGF-A mRNA does not have the potential to be used as a non-invasive diagnostic biomarker.

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