Chemo-enzymatic synthesis, characterization, in vitro antioxidant capacity and oxidative stability studies of novel phosphatidylcholines with ω-3/ω-6 PUFAs and phenolic acids.

Novel phosphatidylcholines containing PUFAs and phenolic acids were synthesized from egg phosphatidylcholine (PC), PUFAs (docosahexaenoic, arachidonic and linoleic acids) and phenolic acids (caffeic, ferulic and p-coumaric acids) as substrates. The structures of modified PCs were confirmed by spectral analysis and were evaluated for antioxidant activities. The modified PCs containing caffeic and ferulic acids exhibited excellent antioxidant activities compared with butylated hydroxytoluene (BHT) and α-tocopherol. The synthesized compounds were also evaluated for the oxidative stabilities in liposome and organic solvent. The modified PCs showed more oxidative stable compared with standard PUFA-PCs and PUFA-PCs + BHT. Results showed that the oxidative stability decreased with increasing degree of unsaturation in organic solvent whereas in liposomes, increased with increasing degree of unsaturation due to tight packed configuration. In this study, phenolic acids were found to render protections for PUFAs in modified PCs from oxidation. Modified PCs may have great potential for applications in food, cosmetic and pharmaceutical industries.

Endothelin 1 gene as a modifier in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is a myocardial disease of unknown etiology with left ventricular dilatation and impaired myocardial contractility leading to heart failure. It is considered to be a multifactorial disorder with the interplay of both genetic and environmental factors. One of the possible genes implicated in DCM is endothelin 1 (EDN1). The genetic variants of EDN1 may be involved in the pathophysiology of DCM hence the entire EDN1 gene was screened to examine for the possible genotypic associations with DCM. A total of 115 DCM patients and 250 control subjects were included in the present study. PCR based SSCP analysis was carried out followed by commercial sequencing. Screening of EDN1 revealed two common and two rare polymorphisms. Allelic and genotypic frequencies were estimated in patient and control groups by appropriate statistical tests. The heterozygotes of insertion variation (+138A) were found to exhibit four-fold increase risk to DCM (OR=4.12, 95% CI 2.10-8.08; p=0.0001). The two rare variants (G>A transition (rs150035515) at c.90 and C>T transition (rs149399492) at c.119) observed in the present study were found to be unique in DCM. The secondary mRNA structures of these variations were found to have less free energy than wild type. The haplotype analysis revealed 4A-T to be risk haplotype for DCM (OR 5.90, 95% CI 2.29-15.25, p=0.0001). In conclusion, EDN1 polymorphisms (+138A, A30A, T40I) appear to play a significant role in the pathogenesis of DCM, as they influence the stability of protein. The increased EDN1 production may lead to constriction of coronary arteries, reducing coronary blood flow which may in turn increase the load on left ventricle, impairing contractility of the heart resulting in a DCM phenotype, an end stage of heart failure.