الفهرس 
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Abstract
Acute myocardial infarction (AMI) is the leading cause of death in the United States. AMI occurs due to underlying coronary artery disease. The occlusion of the coronary artery causes a deprivation of the myocardium from the oxygen supply, which eventually leads to myocardial cell death and necrosis. Despite the incredible progress made in the last two decades in treatment of coronary heart disease and acute myocardial infarction (AMI), AMI is still the most frequent reason for heart failure. Routing conventional biomarkers such as creatine kinase-MB (CK-MB), cardiac troponins (cTns), and lactate dehydrogenase (LDH) were the “gold standard” for AMI diagnosis. The low specificity of elevated cTns affects the diagnosis of AMI as the elevated levels may result from other non-cardiac issues. Additionally, cardiovascular disorders other than AMI may also enhance the release of cTns. Therefore, it is imperative to create biomarkers with high sensitivity and specificity for improving clinical practice, thereby reducing the risk of complications and mortality.
This study included 110 AMI patients admitted to Ain Shams Specialized Hospital, Ain Shams University, Cairo; Egypt. AMI was diagnosed according to WHO criteria including chest pain lasting more than 20 minutes in the previous 24 hours and/or recent ECG abnormalities (new Q-waves and/or ST-segment deviations in two or more contiguous leads on 12 -lead ECG).
Subjects in the present study were classified into the following groups:
group I: Includes 30 healthy control subjects with no family history of CAD, MI, or stroke.
group II: Includes 39 AMI patients without hyperglycemia (HG) nor hypercholesterolemia (HC) [AMI w-].
group III: Includes 38 AMI patients with (HG) [AMI wHG].
group IV: Includes 33 AMI Patients with (HC) [AMI wHC].
Blood samples were the first obtainable samples from patients after admission. from all participants eight milliliters of venous blood specimens were collected from all patients. Each blood sample was divided into two parts; whole blood on EDTA for molecular analysis and glycated hemoglobin A1C (HbA1C) and serum from clotted tubes for the rest of the biochemical investigations. The sera then were separated and divided into several aliquots, and stored at -20oC to be thawed only once on demand for the biochemical analyses. Another 2 ml of fasting venous blood was collected and separated later as mentioned for lipid profile estimation.
All samples were analyzed for determination of the expression levels of lncRNA MIAT and lncRNA TUG1 by qRT-PCR technique, and serum levels of BMP-2, BMP-4, and m-CRP were measured using ELISA technique. The levels of liver function tests (ALT and AST), random blood sugar, glycated hemoglobin A1C, lipid profile (TC, TAG, HDL-C, and LDL-C), and cardiac markers (cTnI, CK-MB, and CK-total) were also estimated.
The purpose of this study was to investigate the diagnostic potential known cardiovascular interrelated lncRNAs such as MIAT and TUG1, in addition to two selected BMPs, BMP2 and BMP4, as well as mCRP as novel biomarkers for AMI.
The results of the present study were clearly indicated that:
AST showed a marked significant elevation in all studied groups comparing to the control, ALT data revealed, non-significant changes in AMI patients without HG or HC, but increased significantly in AMI patients with HG or HC.
As for lipid profile data; TAG, TC, and LDL-C showed a significant elevation, while HDL-C showed a significant decrease in all patient’s groups when compared to the control group.
A highly significant increases in cardiac markers; cTnI and CK-MB were observed in all patient’s groups.
The serum BMP2, BMP4, and mCRP levels increased significantly in all AMI patient groups compared to the controls.
m-CRP correlated positively with MIAT in the control group and correlated negatively with TUG1 in AMI wHG group.
In AMI wHC group, a significant negative correlation was observed between MIAT and TUG1.
The expression levels of lncRNA MIAT and lncRNA TUG1 upregulated significantly in all AMI patients compared to the control.
The ROC curves for BMP-2, BMP-4, and TUG1 showed highest diagnostic performances for all AMI patient’s groups.
The ROC curves for MIAT and m-CRP indicated that they had the lowest utility for the diagnosis.
The AUC of BMP-2 and TUG1 revealed that they were potent biomarkers for AMI patients suffering from HG.
BMP2, BMP4 and TUG1 showed a potential efficacy to discriminate between AMI patients HG from those without, but BMP2 was the most potent biomarker in differentiation. Meanwhile, cardiac troponin (cTnI), MIAT, and m-CRP failed to do this distinguishing.
The AUC increased when BMP-2 was combined with BMP-4 and m-CRP, as well as the combination between MIAT and TUG1 also improved the AUC and increases the potency of biomarkers in the prediction better than any marker alone.
MIAT and TUG1 as well as, BMP-4 were associated with increased risk of AMI even after adjusting age, sex, smoking habits, TG, HDL-C, LDL-C, and the presence of DM as potential confounders.