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51.
Atherosclerosis is a pathologic condition caused by chronic inflammation in response to lipid deposition in the arterial wall. There are many known contributing factors such as long-term abnormal glucose levels, smoking, hypertension, and hyperlipidemia. Under the influence of such factors, immune and non-immune effectors cells are activated and participate during the progression of atherosclerosis. Protein kinase C (PKC) family isoforms are key players in the signal transduction pathways of cellular activation and have been associated with several aspects of the atherosclerotic vascular disease. This review article summarizes the current knowledge of PKC isoforms functions during atherogenesis, and addresses differential roles and disputable observations of PKC isoforms. Among PKC isoforms, both PKCβ and PKCδ are the most attractive and potential therapeutic targets. This commentary discusses in detail the outcomes and current status of clinical trials on PKCβ and PKCδ inhibitors in atherosclerosis-associated disorders like diabetes and myocardial infarction. The risk and benefit of these inhibitors for clinical purposes will be also discussed. This review summarizes what is already being done and what else needs to be done in further targeting PKC isoforms, especially PKCβ and PKCδ, for therapy of atherosclerosis and atherosclerosis-associated vasculopathies in the future. 相似文献
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Sunil Veeravalli Bilal A. Omar Lyndsey Houseman Matthew Hancock Sandra G. Gonzalez Malagon Flora Scott Azara Janmohamed Ian R. Phillips Elizabeth A. Shephard 《Biochemical pharmacology》2014
Flavin-containing monooxygenases (FMOs) of mammals are thought to be involved exclusively in the metabolism of foreign chemicals. Here, we report the unexpected finding that mice lacking Fmos 1, 2 and 4 exhibit a lean phenotype and, despite similar food intake, weigh less and store less triglyceride in white adipose tissue (WAT) than wild-type mice. This is a consequence of enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure (REE). This is fuelled, in part, by increased fatty acid β-oxidation in skeletal muscle, which would contribute to depletion of lipid stores in WAT. The enhanced energy expenditure is attributed, in part, to an increased capacity for exercise. There is no evidence that the enhanced REE is due to increased adaptive thermogenesis; instead, our results are consistent with the operation in WAT of a futile energy cycle. In contrast to FMO2 and FMO4, FMO1 is highly expressed in metabolic tissues, including liver, kidney, WAT and BAT. This and other evidence implicates FMO1 as underlying the phenotype. The identification of a novel, previously unsuspected, role for FMO1 as a regulator of energy homeostasis establishes, for the first time, a role for a mammalian FMO in endogenous metabolism. Thus, FMO1 can no longer be considered to function exclusively as a xenobiotic-metabolizing enzyme. Consequently, chronic administration of drugs that are substrates for FMO1 would be expected to affect energy homeostasis, via competition for endogenous substrates, and, thus, have important implications for the general health of patients and their response to drug therapy. 相似文献
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H.-W. Zhang X. Zhao Y.-L. Guo Y. Gao C.-G. Zhu N.-Q. Wu J.-J. Li 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2018,28(10):980-986
Background and aims
The role of lipoprotein (a) [Lp(a)] in coronary artery diseases (CAD) with special clinical background such as type 2 diabetes mellitus (T2DM) has not been fully determined. The aim of the present study was to investigate the relation of Lp(a) to type 2 diabetic patients with or without CAD.Methods and results
A total of 2040 consecutive patients with T2DM who received selective coronary angiography (CAG) due to angina-like chest pain were enrolled. The patients were subsequently divided into CAD and non-CAD groups according to the results of CAG. The severity of CAD was evaluated by the Gensini Score (GS), number of stenotic vessels, and history of myocardial infarction (MI). Data showed that Lp(a) levels were higher in the CAD group than in the non-CAD group (median: 15.00 mg/dL vs. 11.88 mg/dL, P = 0.025). The results from CAD subgroup analysis indicated that the patients with MI, multiple-vessel disease and high GS had higher Lp(a) levels compared with those in their matched subgroups (P < 0.05, respectively). After adjustment for confounders, Lp(a) levels were independently related to the presence and severity of CAD (CAD:OR = 1.564; MI:OR = 1.523; high GS:OR = 1.388; multiple-vessel disease:OR = 1.455; P < 0.05, respectively).Conclusion
Elevated Lp(a) levels were independently associated with the presence and severity of CAD in patients with T2DM. More studies are necessary to confirm our findings. 相似文献54.
Polymorphisms of microsomal triglyceride transfer protein in different hepatitis B virus-infected patients 总被引:1,自引:0,他引:1
Yang ZT Zhang XX Kong XF Zhang DH Zhang SY Jiang JH Gong QM Jin GD Lu ZM 《World journal of gastroenterology : WJG》2008,14(35):5454-5460
AIM: To identify the two polymorphisms of microsomal triglyceride transfer protein (MTP) gene in the Chinese population and to explore their correlation with both hepatitis B virus (HBV) self-limited infection and persistent infection.
METHODS: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history), matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR).
RESULTS: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkage disequilibrium between H297Q and -493G/T (D' = 0.77). As the χ^2 test was used, the genotype distribution of MTP-493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (χ^2 = 8.543, P = 0.015 and χ^2 = 7.199, P = 0.019). The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (χ^2 = 6.212, P = 0.013). The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897). CONCLUSION: The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated. 相似文献
METHODS: A total of 316 subjects with self-limited HBV infection and 316 patients with persistent HBV infection (195 subjects without familial history), matched with age and sex, from the Chinese Han population were enrolled in this study. Polymorphisms of MTP at the promoter region -493 and at H297Q were determined by the allele specific polymerase chain reaction (PCR).
RESULTS: The ratio of males to females was 2.13:1 for each group and the average age in the self-limited and chronic infection groups was 38.36 and 38.28 years, respectively. None of the allelic distributions deviated significantly from that predicted by the Hardy-Weinberg equilibrium. There was a linkage disequilibrium between H297Q and -493G/T (D' = 0.77). As the χ^2 test was used, the genotype distribution of MTP-493G/T demonstrated a significant difference between the self-limited infection group and the entire chronic group or the chronic patients with no family history (χ^2 = 8.543, P = 0.015 and χ^2 = 7.199, P = 0.019). The allele distribution at the MTP-493 position also demonstrated a significant difference between the study groups without family history (χ^2 = 6.212, P = 0.013). The T allele emerged as a possible protective factor which may influence the outcomes of HBV infection (OR: 0.59; 95% CI: 0.389-0.897). CONCLUSION: The polymorphism of the MTP gene, T allele at -493, may be involved in determining the HBV infection outcomes, of which the mechanism needs to be further investigated. 相似文献
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57.
André J. Tremblay Benoît Lamarche Carolyn F. Deacon S. John Weisnagel Patrick Couture 《Metabolism: clinical and experimental》2014
Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized. 相似文献
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The aim of the study was to explore the effects of 12 weeks daily krill oil supplementation on fasting serum triglyceride (TG) and lipoprotein particle levels in subjects whose habitual fish intake is low and who have borderline high or high fasting serum TG levels (150–499 mg/dL). We hypothesized that Krill oil lowers serum TG levels in subjects with borderline high or high fasting TG levels. To test our hypothesis 300 male and female subjects were included in a double-blind, randomized, multi-center, placebo-controlled study with five treatment groups: placebo (olive oil) or 0.5, 1, 2, or 4 g/day of krill oil. Serum lipids were measured after an overnight fast at baseline, 6 and 12 weeks. Due to a high intra-individual variability in TG levels, data from all subjects in the four krill oil groups were pooled to increase statistical power, and a general time- and dose-independent one-way analysis of variance was performed to assess efficacy. Relative to subjects in the placebo group, those administered krill oil had a statistically significant calculated reduction in serum TG levels of 10.2%. Moreover, LDL-C levels were not increased in the krill oil groups relative to the placebo group. The outcome of the pooled analysis suggests that krill oil is effective in reducing a cardiovascular risk factor. However, owing to the individual fluctuations of TG concentrations measured, a study with more individual measurements per treatment group is needed to increase the confidence of these findings. 相似文献