BackgroundHypertrophic Cardiomyopathy (HCM) is a complex myocardial disorder with a recognized genetic heterogeneity. The elevated number of genes and mutations involved in HCM limits a gene-based diagnosis that should be considered of most importance for basic research and clinical medicine.MethodologyIn this report, we evaluated High Resolution Melting (HRM) robustness, regarding HCM genetic testing, by means of analyzing 28 HCM-associated genes, including the most frequent 4 HCM-associated sarcomere genes, as well as 24 genes with lower reported HCM-phenotype association. We analyzed 80 Portuguese individuals with clinical phenotype of HCM allowing simultaneously a better characterization of this disease in the Portuguese population.ResultsHRM technology allowed us to identify 60 mutated alleles in 72 HCM patients: 49 missense mutations, 3 nonsense mutations, one 1-bp deletion, one 5-bp deletion, one in frame 3-bp deletion, one insertion/deletion, 3 splice mutations, one 5'UTR mutation in MYH7, MYBPC3, TNNT2, TNNI3, CSRP3, MYH6 and MYL2 genes. Significantly 22 are novel gene mutations.ConclusionsHRM was proven to be a technique with high sensitivity and a low false positive ratio allowing a rapid, innovative and low cost genotyping of HCM. In a short return, HRM as a gene scanning technique could be a cost-effective gene-based diagnosis for an accurate HCM genetic diagnosis and hopefully providing new insights into genotype/phenotype correlations.
Transforming growth factor (TGF)- and des-Arg10 -kallidin stimulate the expression of connective tissue growth factor (CTGF), a matrix signaling molecule that is frequently overexpressed in fibrotic disorders. Because the early signal transduction events regulating CTGF expression are unclear, we investigated the role of Ca
/Ca2؉ exchanger in fibrogenesis, we also observed that KB-R7943 likewise blocked TGF-1-stimulated levels of CTGF mRNA in human microvascular endothelial and human osteoblast-like cells. We conclude that Ca 2؉ entry mode operation of the Na ؉ /Ca 2؉ exchanger is required for des-Arg 10
Flavonoids are naturally occurring plant compounds with antioxidant properties. Their consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Low-density lipoprotein (LDL) oxidative modification is currently thought to be a significant event in the atherogenic process. Most of the experiments concerning the inhibition of LDL oxidation used isolated LDL. We used diluted human whole plasma to study the influence of flavonoids on lipid peroxidation (LPO) promoted by copper, and their interaction with uric acid, one of the most important plasma antioxidants. Lipid peroxidation was evaluated by the formation of thiobarbituric acid reactive substances (TBARS) and of free malondialdehyde (MDA). The comparative capability of the assayed flavonoids on copper (II) reduction was tested using the neocuproine colorimetric test. In our assay system, urate disappears and free MDA and TBARS formation increase during the incubation of plasma with copper. Most of the tested flavonoids inhibited copper-induced LPO. The inhibition of LPO by flavonoids correlated positively with their capability to reduce copper (II). The urate consumption during the incubation of plasma with copper was inhibited by myricetin, quercetin and kaempferol. The inhibition of urate degradation by flavonoids correlated positively with the inhibition of LPO. Urate inhibited the copper-induced LPO in a concentration-dependent mode. Luteolin, rutin, catechin and quercetin had an antioxidant synergy with urate. Our results show that some flavonoids could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and some of the flavonoids.
Background: There is accumulating evidence from the epidemiological field of telomere biology that telomere length plays an important role in the pathophysiology of cardiovascular disease. The RNA-dependent DNA polymerase, telomerase, is essential in regulating telomere length by acting as a reverse transcriptase. However, the relationship between telomerase activity and telomere length in cardiovascular disease is unclear. This is due, in part, to the paucity of information on the utility of a quantitative and routine assay for the determination of telomerase activity in circulating blood leukocytes. Methods: We used a validated, high-sensitive realtime quantitative telomeric repeat amplification protocol (RQ-TRAP) to determine telomerase activity in circulating blood leukocytes.Results: The present investigation demonstrated direct and reliable detection of telomerase activity of circulating blood leukocytes.
Conclusion:The present investigation suggests the feasibility of using RQ-TRAP assay in routine screening of telomerase activity in blood specimens typically collected in a clinical/epidemiological setting.
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