Introduction:We have previously demonstrated the ability of retinoic acid to regulate the expression the atrial specific markers AMHC-1 and Tbx5 during early cardiac chamber specification.However, the molecular mechanisms responsible for this process still remain unclear.At present, microRNAs represent a novel layer of complexity in the regulatory networks controlling gene expression during cardiovascular development.Purpose: The aim of this work is to study the intrinsic mechanism involved in this signaling pathway, since miR-133 has demonstrated to be involved in other earliest cardiac developmental processes.Methods: Our model is focused on developing chick at gastrula stages by in vitro electroporation of miR-133, a microRNA which is has been shown expressed at the level of linear cardiac tube.Results: Our results show the miR-133 expression at the level of the primitive heart tube.Moreover, or work reveals that overexpression of miR-133 suppresses AMHC-1 and Tbx5 expression.Conclusion: These data support that miR-133, a putative microRNA that targets RARB 3 ´UTR, regulates the early cardiac chamber specification via retinoic acid pathway.
The exercise stress test (EST) is the commonest non-invasive test to elucidate the nature of chest pain/discomfort. ST segment depression provides evidence of ischemia, but is hampered by a significant number of false negative and false positive tests. This study evaluated patterns and duration of ST depression in an attempt to differentiate false positive and false negative tests. One hundred consecutive patients with suspected angina referred to the Cardiac Clinic, who underwent an EST, and subsequently a coronary angiogram, were studied. The EST was classified as positive if significant ST depression (greater than 1mm 80msec after the J point) developed during exercise or the recovery phase. Based on the angiographic findings as the reference, the EST was classified as true positive (TP), true negative (TN), false positive (FP) or false negative (FN). Onset, magnitude and type of ST depression in relation to disease, the recovery time (RT), total ischemic time (TIT) and time-course patterns in TP versus FP results were compared by Chi square test. The EST was positive in 77 patients (true positive n = 65; false positive n = 12). The angiographic findings were classified as normal (17), non-occlusive atheroma (10) and as significant coronary stenosis in the remainder. Though the mean time to ST recovery (IRT) was shorter (183 + 118sec) in subjects with false positive compared to true positive (264 + 116sec) p<0.05, it was over three minutes and did not really help in differentiating FP from TP tests. TIT was more reliable than the IRT in delineating true positive from false positive tests. Up-sloping ST changes were more commonly associated with false positivity. Time-course patterns could not reliably distinguish TP from FP tests (TIT = 8/12, RT = 7/12), but TIT was more reliable in verifying TP (64/65) tests than IRT (59/65).KEY WORDS: Exercise stress test; ST segment time course patterns
Purpose: We investigated gene polymorphisms related to oxidative stress and dyslipidaemia in a sample of subjects with and without metabolic syndrome (MS) from the Phoenix Lifestyle project. Single nucleotide polymorphisms (SNP) in the Human Paraoxonase /PON1 ( Leu55Met and Gln192Arg SNPs) and LPL genes (N291S and S447X SNPs) were studied to investigate the associations of these mutations with cardiovascular risk factors and risk factor clustering in this sample.
Method: There were 1419 subjects from the Phoenix Lifestyle Project cohort who were studied for CV risk factor prevalence and clustering. Anthropometric measurements were performed, with fasting venous blood samples taken from each subject for glucose, lipid and genetic analysis. Genotyping was performed using real-time PCR, allele-specific probes and Melting Curve analysis in a sample of 916 subjects.
Results: The crude prevalence of MS in this sub-cohort, classified according to the IDF criteria was 50%. The LPL and PON 1 genotypes were similarly distributed (p = n/s) in subjects with and without MS. There were no subjects observed with the LPL N291S mutation. There was a significant interaction between the Gln192Arg genotype and elevated triglyceride (> 1.7 mmol/l) levels (p=0.016; OR = 1.356), and in overweight females (BMI>23kg/m2) (p=0.027; OR = 1.911), which was identified in 23% of overweight females.
Discussion: Our study did not support a role for these polymorphisms for predisposition to the MS. Although the S447X, L55M and Q192R polymorphisms are common in this population, only the 192Arg allele, previously associated with reduced protection against lipid peroxidation, predispose to hypertriglyceridaemia in the population, and general obesity in females. Gene polymorphisms related to the MS risk factors may explain a high predisposition to premature atherosclerosis.