Coding SNPs in hsa-miR-1343-3p and hsa-miR-6783-3p target sites of CYP2C19 modulates clopidogrel response in individuals with cardiovascular diseases.

AIMS: To investigate the impact of microRNA target SNPs (mirSNPs) and their interaction with miRNAs on important drug-metabolizing enzymes, transporters and target genes for prediction of clopidogrel drug response in cardiovascular disease individuals. MAIN METHODS: A prospective cross-sectional study was conducted on 292 individuals undergoing clopidogrel drug therapy. All the enrolled participants were administered 300 mg loading dose followed by 75 mg dose of maintenance therapy. Platelet aggregations were measured before administration of the loading dose and 2 h post fifth day dose of clopidogrel maintenance therapy. Clopidogrel carboxylic acid metabolite from plasma and urine were analyzed post maintenance therapy using the RP-HPLC method. Genotyping of mirSNP's shortlisted through in silico analysis was performed by tetra ARMS PCR and validated by Sanger DNA sequencing. The levels of selected miRNAs were estimated by the TaqMan-PCR assay. Functional validation of mirSNPs was performed in HepG2 cells after transfecting with the selected gene and miRNA mimics. Protein expressions were analyzed by western blot. KEY FINDINGS: 23% of enrolled individuals showed resistance to clopidogrel therapy. Out of 13 mirSNP's analyzed, CYP2C19 rs4244285 was associated with clopidogrel drug resistance and clopidogrel carboxylic acid metabolite in urine and plasma. hsa-miR-1343-3p and hsa-miR-6783-3p levels were significantly high in individuals with CYP2C19 rs4244285 mutant genotype and these miRNAs down-regulated the protein expression of CYP2C19. SIGNIFICANCE: We demonstrated the role of coding mirSNP (rs4244285) in the regulation of the CYP2C19 gene through miRNAs and its implications to clopidogrel drug response prediction in the Indian population.

Percutaneous intervention for symptomatic central vein stenosis in patients with upper limb arteriovenous dialysis access.

Central venous stenosis is an important hindrance to long-term maintenance of arteriovenous access in the upper extremities in dialysis patients. AIM: The present study was done to determine feasibility and clinical success of endovascular approach for the treatment of symptomatic central venous stenosis associated with significant ipsilateral limb edema in dialysis patients with vascular access in the upper limb. METHODS: A database of hemodialysis patients who underwent endovascular treatment for central venous stenosis from January 2014 to January 2017 at our institute was retrospectively reviewed. Follow-up was variable. RESULTS: The study included ten patients (6 men and 4 women) with a mean age of 45.2 years, who underwent thirteen interventions during a period of 3 years. The technical success rate for endovascular treatment was 100%. One patient underwent primary PTA (percutaneous transluminal angioplasty). Seven patients underwent primary PTA and stenting. Three patients underwent secondary PTA. One among these patients underwent secondary PTA twice along with fistuloplasty. One patient underwent secondary PTA with stenting. No immediate complications were encountered during the procedure. Our study shows a primary patency rate of 67% and 33% at 6 months and 12 months for PTA with stenting. Our study also shows secondary or assisted primary patency of 75% at 6 months of follow-up. CONCLUSIONS: Endovascular therapy (PTA) with or without stenting for central venous stenosis is safe, with low rates of technical failure. Multiple additional interventions are the rule and long-term patency rate is not very good.

Prinzmetals Angina Masquerading as Acute Pericarditis.

Coronary artery spasm is an intense vasoconstriction of the coronary arteries and may be responsible for the myocardial ischemia, myocardial infarction as well as sudden deaths. Coronary angiography is generally needed to identify the cause. Coronary artery spasm is a multifactorial disease with underlying mechanism still poorly understood. Here, we present case of a 48-year-old male with no significant past history who presented with acute episodic onset chest pain. Clinical, Electrocardiography (ECG) and echocardiographic findings suggested pericarditis but a diagnostic coronary angiography revealed significant coronary vasospasm. Patient's symptoms significantly improved with calcium channel blockers and Nitroglycerine (NTG).