Association of Increased Levels of lncRNA H19 in PBMCs with Risk of Coronary Artery Disease.

OBJECTIVE: Considerable research shows that long non-coding RNAs, those longer than 200 nucleotides, are involved in several human diseases such as various cancers and cardiovascular diseases. Their significant role in regulating the function of endothelial cells, smooth muscle cells, macrophages, vascular inflammation, and metabolism indicates the possible effects of lncRNAs on the progression of atherosclerosis which is the most common underlying pathological process responsible for coronary artery disease (CAD). The aim of present study was to assess whether the expression of the lnc RNA H19 was associated with a susceptibility to CAD by evaluating the expression level of H19 in the peripheral blood. MATERIALS AND METHODS: A case-control study of 50 CAD patients and 50 age and sex-matched healthy controls was undertaken to investigate whether the H19 lncRNA expression level is associated with a CAD using Taqman Real-Time polymerase chain reaction (PCR). RESULTS: The subsequent result indicated that the H19 lncRNA was over-expressed in CAD patients in comparison with the controls. However, it was not statistically significant. This overexpression may be involved in coronary artery disease progression. CONCLUSION: We report here, the up-regulation of H19 lncRNA in the whole blood of CAD patients and suggest a possible role for H19 in the atherosclerosis process and its consideration as novel biomarker for CAD.

Association between Long Noncoding RNA ANRIL Expression Variants and Susceptibility to Coronary Artery Disease.

Animal cells possess thousands of long non-coding (lnc) RNAs, such as antisense noncoding RNA in the INK4 locus (ANRIL), which have regulatory roles in the cells' molecular mechanisms, including X-chromosome inactivation, and developmental processes. These lnc RNAs are known to influence the extensive spectrum of age-related disorders. Accordingly, there is evidence for the role of these lnc RNAs in cardiovascular diseases, particularly coronary artery diseases (CAD). The aim of this study was to assess whether the expression of the lnc RNA ANRIL was associated with a susceptibility to CAD by evaluating the expression level of the two transcripts of ANRIL. Peripheral blood was taken from fifty patients affected by CAD and relative expression of ANRIL was determined by Real-Time PCR assay. The obtained data indicated that the EU741058 transcript expression level significantly decreased in CAD patients in comparison with the healthy individuals (P= 0.001). Furthermore, there was no significant association between the NR_003529 transcript expression, and CAD risk in Iranian patients (P=0.751). Our results suggest that the expression level of the EU741058 transcript of ANRIL may be implicated in CAD development, creating a predictive biomarker for CAD patients in future.

Effects of N-acetylcysteine on the cardiac remodeling biomarkers and major adverse events following acute myocardial infarction: a randomized clinical trial.

AIMS: The aims of this study were to evaluate the effects of N-acetylcysteine (NAC) on cardiac remodeling and major adverse events following acute myocardial infarction (AMI). METHODS: In a prospective, double-blind, randomized clinical trial, the effect of NAC on the serum levels of cardiac biomarkers was compared with that of placebo in 98 patients with AMI. Also, the patients were followed up for a 1-year period for major adverse cardiac events (MACE), including the occurrence of recurrent myocardial infarction, death, and need for target vessel revascularization. RESULTS: In patients who received NAC, the serum levels of matrix metalloproteinase (MMP)-9 and MMP-2 after 72 h were significantly lower than those in the placebo group (p = 0.014 and p = 0.045, respectively). The length of hospitalization in patients who received NAC was significantly shorter than that in the placebo group (p = 0.024). With respect to MACE, there was a significant difference between those who received NAC (14 %) and those patients on placebo (25 %) (p = 0.024). Re-infarction took place in 4 % of patients in the NAC group as compared with 16.7 % in patients who received placebo (p = 0.007). CONCLUSION: NAC can be beneficial in preventing early remodeling by reducing the level of MMP-2 and MMP-9. Moreover, NAC decreased the length of hospital stays in patients after AMI. By decreasing MACE, NAC could possibly be introduced as a 'magic bullet' in the pharmacotherapy of patients with AMI. Further studies are needed to elucidate NAC's role in this population.

N-Acetylcysteine effects on transforming growth factor-ß and tumor necrosis factor-α serum levels as pro-fibrotic and inflammatory biomarkers in patients following ST-segment elevation myocardial infarction.

BACKGROUND AND AIMS: Ischemia following acute myocardial infarction (AMI) increases the level of pro-fibrotic and inflammatory cytokines, including transforming growth factor (TGF)-ß and tumor necrosis factor (TNF)-α. N-acetylcysteine (NAC) has therapeutic benefits in the management of patients with AMI. To the best of our knowledge, this is the first study that has evaluated the effect of NAC on TNF-α and TGF-ß levels in patients with AMI. METHODS: Following confirmation of AMI, 88 patients were randomly administered NAC 600 mg (Fluimucil(®), Zambon, Ticino, Switzerland) or placebo orally twice daily for 3 days. For quantification of TGF-ß and TNF-α serum levels after 24 and 72 h of NAC or placebo administration, peripheral venous blood (10 mL) samples were collected at these time points. RESULTS: Comparisons between levels of TGF-ß and TNF-α after 24 and 72 h within the NAC or placebo groups revealed that there was not any significant difference except for TGF-ß levels in the placebo group, which increased significantly over time (p = 0.042). Significant relationships existed between patients' ejection fraction (p = 0.005) and TGF-ß levels. CONCLUSIONS: Receiving NAC could prevent TGF-ß levels from increasing after 72 h as compared with not receiving NAC. As TGF-ß had strong correlations with the ejection fraction, its antagonism seems to be important in the prevention of remodeling.

Multiple inflammatory prognostic factors in acute coronary syndromes: a prospective inception cohort study.

Inflammatory basis in pathopoiesis of coronary artery disease (CAD) have been demonstrated in recent decades. Elevated C-Reactive Protein (CRP) and leukocytosis were associated with an elevated risk for acute coronary syndrome (ACS). To evaluate the relationship between quantitative CRP and cardiac troponin I in conjunction with white blood cell (WBC) count and 30 days outcomes and treatment planning in patients with ACS. A concurrent inception cohort study was designed involving 200 patients as exposed and 200 patients as non exposed groups. We evaluated the relationship between baseline CRP and WBC count and cardiac troponin I , other risk factors and biomarkers, angiographic and other para-clinical tests and clinical outcomes with ACS. Higher CRP and WBC count were associated with additional coronary care unite (CCU) admission days (P = 0.002), hospitalization days (P = 0.007), arrhythmia type (P = 0.007), receiving streptokinase (P = 0.001), angiographic findings (P = 0.003), final myocardial infarction versus unstable angina (P = 0.001), date of complication (P = 0.001) and the date of cardiopulmonary resuscitation (if incident) (P = 0.015). In a multivariate Cox proportional hazard model high CRP and WBC count remained strong predictor of mortality (P = 0.028), angiography findings (three Vessel disease (3VD) and left main (LM) disease) (P = 0.001), and readmission in CCU (P = 0.002). A cardiac troponin I above 0.1 microg/lit was considered elevated. Elevated troponin level, demonstrated a significant relationship with MI incidence between two groups (P = 0.001) (89% in troponin positive group versus 11% in troponin less than 0.1 microg/lit). Inflammatory markers including, CRP and WBC count can be used to predict mortality, readmission, 3VD and LM disease in patients with ACS. In a Cox Proportional Hazard Model cardiac troponin above 0.1 microg/lit was significant predictors of MI (P = 0.003) and CPR (P = 0.044) at 30 days follow up period.