Farshad Shakerian

Coronary artery disease (CAD), the leading cause of mortality globally, arises from atherosclerotic blockage of the coronary arteries. Meta-vinculin (meta-VCL), a large spliced isoform of VCL, co-localizes in muscular adhesive structures and plays significant roles in cardiac physiology and pathophysiology. This study aimed to identify microRNAs (miRNAs) regulating meta-VCL expression and investigate the expression alterations of the miRNAs of interest and meta-VCL as potential biomarkers in the serum of CAD patients. Bioinformatics tools were employed to select miRNAs targeting meta-VCL. Cell-based ectopic expression analysis and a dual-luciferase assay were used to examine the interactions between miRNAs and meta-VCL. An ELISA assessed the concentrations of interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α (TNF-α). MiRNA and meta-VCL expression patterns and biomarker suitability were evaluated in serum samples from CAD and non-CAD individuals using real-time PCR. A cardiac cell-line data set and CAD blood exosome samples were analyzed using bioinformatics and ROC curve analyses, respectively. miR-6721-5p directly interacted with the putative target sites at the 3'-UTR of meta-VCL and regulated its expression. IL-10 and TNF-α concentrations, which may act as anti-inflammatory factors, decreased following miR-6721-5p upregulation and meta-VCL downregulation. Bioinformatics and experimental expression analyses confirmed downregulated meta-VCL expression and upregulated miR-6721-5p expression in CAD samples. ROC curve analysis yielded an AUC score of 0.705 (P = 0.018), indicating the potential suitability of miR-6721-5p as a biomarker for CAD. miR-6721-5p plays a regulatory role in meta-VCL expression and may contribute to CAD development by reducing anti-inflammatory factors. These findings suggest that miR-6721-5p could serve as a novel biomarker in the pathogenesis of CAD.

Contrast-induced acute kidney injury (CI-AKI) is an adverse consequence of percutaneous coronary interventions which results in significant morbidity and mortality and adds to the costs of diagnostic and interventional cardiology procedures. Various pathophysiological mechanisms have been proposed for CI-AKI and various agents tested for its prevention. There is currently a general agreement that adequate pre-procedural hydration constitutes the cornerstone of prevention, yet there are reports of the use of some other agents with various efficacies. We prospectively tested IV magnesium sulfate (Mg) for CI-AKI prevention. This study is a prospective, randomized, open-labeled, single-center clinical trial. We randomly assigned 122 consecutive patients to two groups. The first group was the control group with routine treatment (n = 64), and second group was the study group with routine treatment plus IV magnesium sulfate 1 g just before the procedure (n = 62). Serum creatinine was measured before the procedure and 2 days after the procedure. The primary end point was the occurrence of CI-AKI within 48 h. CI-AKI was defined as 0.5 mg/dl or more increase in serum creatinine or 25 % or more increase above baseline serum creatinine. There was no difference in definition if both of these parameters were present. The control and study groups were comparable in the overall predicted risk of CI-AKI. Also, the type and volume of the contrast were not significantly different between the two groups. Following angioplasty, CI-AKI occurred in 17 (26.6 %) patients in the control group and nine (14.5 %) patients in the study group; there was a significant reduction in CI-AKI in the study group (P = 0.01). Additionally, there was no mortality or a need for hemodialysis in either group. In primary PCI patients, the prophylactic use of intravenous Mg can be recommended to be added to traditional hydration for CI-AKI prevention.

Thrombotic thrombocytopenic purpura (TTP) is a rare syndrome affecting multiple organs. There is no sufficient evidence regarding the clinical cardiac manifestations of TTP. Nonetheless, pathologic cardiac involvement is quite frequent in acute TTP, which is predominantly manifested as myocardial necrosis due to coronary arteriolar microthrombosis. The present case report describes a 43-year-old man with long-standing remitted TTP, who suffered from a sequence of refractory thrombotic epicardial coronary events. Aggressive medical and interventional therapies, including long-term dual antiplatelets and coronary angioplasty, were finally successful in remitting the thrombotic events. During his two-year follow up, he has been asymptomatic.

Coronary artery disease (CAD) is the leading cause of mortality in many parts of the world. Genome-wide association studies (GWAS) have identified several genetic variants associated with CAD in Low-density lipoprotein receptor (LDLR) locus. This study was evaluated the possible association of genetic markers at LDLR locus with CAD irrespective to lipid profile and as well as the association of these SNPs with severity of CAD in Iranian population. Sequencing of 2 exons in LDLR gene (Exon 2, 12) and part of intron 30 of SMARCA4 gene include rs1122608, was performed in 170 Iranian patients angiographically confirmed CAD and 104 healthy controls by direct sequencing. Sullivan's scoring system was used for determining the severity of CAD in cases. Our results showed that homozygote genotypes of rs1122608 (P<0.0001), rs4300767 (P<0.005) and rs10417578 (p<0.007) SNPs have strong protective effects on the CAD. In addition, we found that rs1122608 (GT or TT) was at higher risk of three vessel involvement compared to single vessels affecting (P=0.01).

Significant elevation of cardiac biomarkers after percutaneous coronary intervention (PCI) is associated with increased mortality. However, clinical importance of lesser degrees of cardiac enzyme elevation has not been well understood. Multiple factors might have an etiologic role, and the incidence of myonecrosis has not changed dramatically despite pharmacological and technological advances in PCI. The aim of this study was to evaluate the role of intracoronary (IC) Adenosine in preventing the elevation of cardiac enzymes as a marker of myonecrosis after PCI in patients with chronic stable angina. Two hundred sixty patients with chronic stable angina who were candidates for PCI were randomly assigned to double-blinded pretreatment with IC Adenosine or placebo before crossing of the guide wire. The patients were observed during the hospital course, and blood samples were obtained in standard intervals after the intervention for cardiac biomarkers. The primary end point of this study was post-PCI myonecrosis, and secondary end point was safety of IC Adenosine administration in the setting of PCI in patients with chronic stable angina. Of the 260 patients, who were initially randomized, finally 83 patients were analyzed in the placebo and 96 in the Adenosine arms. The study patients were comparable in clinical and angiographic characteristics. The mean of the patients’ age was 57.3 years (range = 35 to 79 years), and 71.5% were male. There were no differences in the mean serum cardiac biomarkers between the study groups (mean creatine kinase-MB [CK.MB] level of 29.5 ± 14.5 IU/L in the placebo group and 31.5 ± 18.5 IU/L in the control group; p value = 0.41; mean cardiac troponin I (cTnI) level of 0.097 ± 0.178 μg/L in the placebo group and 0.167 ± 0.5 μg/L in the control group; p value = 0.24). Despite promising results in primary PCI, our study showed that a strategy of IC Adenosine pretreatment is not beneficial in reducing post-PCI myonecrosis in patients with chronic stable angina and should not be routinely used.