Aim: The objective of this study was to examine the effects of n-3 polyunsaturated fatty acids (n-3 PUFAs)on coronary arterial large conductance Ca²⁺-activated K⁺ (BK) channel function in coronary smooth muscle cells (SMCs) of streptozotocin-induced diabetic rats. Methods: The effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on coronary BK channel open probabilities were determined using the patch clamp technique. The mRNA and protein expressions of BK channel subunits were measured using qRT-PCR and Western blots. The coronary artery tension and coronary SMC Ca²⁺ concentrations were measured using a myograph system and fluorescence Ca²⁺ indicator. Results: Compared to nondiabetic control rats, the BK channel function was impaired with a reduced response to EPA and DHA in freshly isolated SMCs of diabetic rats. Oral administration of n-3 PUFAs had no effects on protein expressions of BK channel subunits in nondiabetic rats, but significantly enhanced those of BK-β₁ in diabetic rats without altering BK-α protein levels. Moreover, coronary ring tension induced by iberiotoxin (a specific BK channel blocker) was increased and cytosolic Ca²⁺ concentrations in coronary SMCs were decreased in diabetic rats, but no changes were found in nondiabetic rats. Conclusions: n-3 PUFAs protect the coronary BK channel function and coronary vasoreactivity in diabetic rats as a result of not only increasing BK-β₁ protein expressions, but also decreasing coronary artery tension and coronary smooth muscle cytosolic Ca²⁺ concentrations.

Objective. The metabolism of three major nutrients (sugar, lipid, and protein) will change during pregnancy, especially in the second trimester. The present study is aimed at evaluating carnitine alteration in fatty acid metabolism in the second trimester of pregnancy and the correlation between carnitine and GDM. Methods. 450 pregnant women were recruited in the present prospective study. Metabolic profiling of 31 carnitines was detected by LC-MS/MS in these women. Correlation between carnitine metabolism and maternal and neonatal complication with GDM was analyzed. Results. We found the levels of 7 carnitines increased in age>35, BMI≥30, weight gain>20 kg, and ART pregnant groups, but the level of free carnitine (C0) decreased. Nine carnitines were specific metabolites of GDM. Prepregnancy BMI, weight gain, and carnitines (C0, C3, and C16) were independent risk factors associated with GDM and related macrosomia. C0 was negatively correlated with FBG, LDL, TG, and TC. A nomogram was developed for predicting macrosomia in GDM based on carnitine-related metabolic variables. Conclusion. The carnitine metabolism in the second trimester is abnormal in GDM women. The dysfunction of carnitine metabolism is closely related to the abnormality of blood lipid and glucose in GDM. Carnitine metabolism abnormality could predict macrosomia complicated with GDM.

Aim: Docosahexaenoic acid (DHA) is known to activate the vascular large-conductance calcium-activated potassium (BK) channels and has protective effects on the cardiovascular system. However, the underlying mechanisms through which DHA activates BK channels remain unclear. In this study, we determined such mechanisms by examining the effects of different concentrations of DHA on BK channels in freshly isolated rat coronary arterial smooth muscle cells (CASMCs) using patch clamp techniques.Methods and Results: We found that BK channels are the major potassium currents activated by DHA in rat CASMCs and the effects of DHA on BK channels are concentration dependent with a bimodal distribution. At concentrations of <1 μM, DHA activated whole-cell BK currents with an EC50 of 0.24 ± 0.05 μM and the activation effects were abolished by pre-incubation with SKF525A (10 μM), a cytochrome P450 (CYP) epoxygenase inhibitor, suggesting the role of DHA-epoxide. High concentrations of DHA (1–10 μM) activated whole-cell BK currents with an EC50 of 2.38 ± 0.22 μM and the activation effects were unaltered by pre-incubation with SKF525A. Single channel studies showed that the open probabilities of BK channels were unchanged in the presence of low concentrations of DHA, while significantly increased with high concentrations of DHA. In addition, DHA induced a dose-dependent increase in cytosolic calcium concentrations with an EC50 of 0.037 ± 0.01 μM via phospholipase C (PLC)–inositol triphosphate (IP3)–Ca2+ signal pathway, and inhibition of this pathway reduced DHA-induced BK activation.Conclusion: These results suggest that DHA can activate BK channels by multiple mechanisms. Low concentration DHA-induced BK channel activation is mediated through CYP epoxygenase metabolites, while high concentration DHA can directly activate BK channels. In addition, DHA at low and high concentrations can both activate BK channels by elevated cytosolic calcium through the PLC–IP3–Ca2+ signal pathway.

Objective Dyslipidemia in the second trimester and associated gestational diabetes are increasing worldwide. Carnitine plays a key role in lipid metabolism. We aim to describe metabolic profiling in the second trimester based on carnitine related metabolomics in GDM and high risk pregnancy, and to find the potential risk factors in GDM and candidate metabolites for diagnosing GDM induced macrosomia.Methods We have randomly investigated 450 pregnant women and their neonates in this retrospective study and 56 (12.4%) GDM cases were diagnosed. We used LC-MS/MS performing metabolic profiling about 12 amino acids and 31 acylcarnitines (containing C0) to assess circulating metabolites concentration in different subgroup according maternal and newborn clinical characteristic. We also calculated the correlation coefficient between maternal and newborn. GDM potential metabolic risk factors were screened by PLS-DA. Multivariate regression analyses were used in identifying independent risk factors for GDM and macrosomia. Based on these carnitine-related factors, a nomogram for estimating macrosomia was developed.Results We found 14 AA (Ala, Arg, Met, BCAA, AAA) and AC (C0, C2, C3, C4DC+C5OH, C5, C16, C18, C18:1) were increased in Age > 35 group, BMI ≥ 30, weight gain > 20 kg group, using assistant reproductive technology group, but the level of C0, Gly were decreased. In fetal clinical data, we obtained AA and AC level in fetuses are higher than their mothers and the metabolic trend was similar with maternal result. PLS-DA showed 15 metabolism(C0, LEU+ILE+PRO-OH, Phe, C18, TYR, etc)play main roles in class separation of GDM. Multivariate analysis showed pre-pregnancy BMI, weight gain, LEU+ILE+PRO-OH, TYR, C0/acylcarnitine, C0, C3, C16, C18 are independent risk factors associated with GDM. Finally, we developed a nomogram predicting macrosomia based on carnitine-related metabolic variables.Conclusion Metabolomics was proved as a powerful tool in identifying the metabolic alteration during the second trimester. These metabolic risk factors in GDM may help understanding of the underlying biochemical pathology of GDM and help physician diagnosing macrosomia.