The aim of this study was to determine the relationship between lipoprotein(a) Lp(a) and cardiovascular disease (CVD) in a large cohort of patients with heterozygous familial hypercholesterolemia ...(FH).
Lp(a) is considered a cardiovascular risk factor. Nevertheless, the role of Lp(a) as a predictor of CVD in patients with FH has been a controversial issue.
A cross-sectional analysis of 1,960 patients with FH and 957 non-FH relatives recruited for SAFEHEART (Spanish Familial Hypercholesterolemia Cohort Study), a long-term observational cohort study of a molecularly well-defined FH study group, was performed. Lp(a) concentrations were measured in plasma using an immunoturbidimetric method.
Patients with FH, especially those with CVD, had higher Lp(a) plasma levels compared with their unaffected relatives (p < 0.001). A significant difference in Lp(a) levels was observed when the most frequent null and defective mutations in LDLR mutations were analyzed (p < 0.0016). On multivariate analysis, Lp(a) was an independent predictor of cardiovascular disease. Patients carrying null mutations and Lp(a) levels >50 mg/dl showed the highest cardiovascular risk compared with patients carrying the same mutations and Lp(a) levels <50 mg/dl.
Lp(a) is an independent predictor of CVD in men and women with FH. The risk of CVD is higher in those patients with an Lp(a) level >50 mg/dl and carrying a receptor-negative mutation in the LDLR gene compared with other less severe mutations.
Scope
Dysbiosis of gut microbiota is involved in metabolic syndrome (MetS) development, which has a different incidence between men (M) and women (W). The differences in gut microbiota in MetS ...patients are explored according to gender, and whether consuming two healthy diets, Mediterranean (MED) and low‐fat (LF), may, over time, differentially shape the gut microbiota dysbiosis according to gender is evaluated.
Materials and Methods
All the women from the CORDIOPREV study whose feces samples were available and a similar number of men, matched by the main metabolic variables (N = 246, 123 women and 123 men), and categorized according to the presence or not of MetS are included. Gut microbiota is analyzed at baseline and after 3 years of dietary intervention.
Results
Higher abundance of Collinsella, Alistipes, Anaerotruncus, and Phascolarctobacterium genera is observed in MetS‐W than in MetS‐M, whereas the abundance of Faecalibacterium and Prevotella genera is higher in MetS‐M than in MetS‐W. Moreover, higher levels of Desulfovibrio, Roseburia, and Holdemania are observed in men than in women after the consumption of the LF diet.
Conclusion
The results suggest the potential involvement of differences in gut microbiota in the unequal incidence of metabolic diseases between genders, and a sex‐dependent effect on shaping the gut microbiota according to diet.
Dysbiosis of gut microbiota is involved in the development of metabolic syndrome, whose incidence is different between men and women. This work provides evidence of a different gut microbiota composition in metabolic syndrome, according to gender. Moreover, the study shows a differential shaping of the gut microbiota according to the gender in metabolic syndrome patients after the consumption of a Mediterranean or a low‐fat diet for three years.
Apart from its main function in the mitochondria as a key element in electron transport, Coenzyme Q10 (CoQ10) has been described as having multiple functions, such as oxidant action in the generation ...of signals and the control of membrane structure and phospholipid and cellular redox status. Among these, the most relevant and most frequently studied function is the potent antioxidant capability of its coexistent redox forms. Different clinical trials have investigated the effect of CoQ10 supplementation and its ability to reduce oxidative stress. In this review, we focused on recent advances in CoQ10 supplementation, its role as an antioxidant, and the clinical implications that this entails in the treatment of chronic diseases, in particular cardiovascular diseases, kidney disease, chronic obstructive pulmonary disease, non-alcoholic fatty liver disease, and neurodegenerative diseases. As an antioxidant, CoQ10 has proved to be of potential use as a treatment in diseases in which oxidative stress is a hallmark, and beneficial effects of CoQ10 have been reported in the treatment of chronic diseases. However, it is crucial to reach a consensus on the optimal dose and the use of different formulations, which vary from ubiquinol or ubiquinone Ubisol-Q10 or Qter®, to new analogues such as MitoQ, before we can draw a clear conclusion about its clinical use. In addition, a major effort must be made to demonstrate its beneficial effects in clinical trials, with a view to making the implementation of CoQ10 possible in clinical practice.
Circulating microparticles (cMPs) seem to play important roles in vascular function. Beyond markers of activated cells, cMPs may have potential paracrine functions and influence atherosclerosis. ...Here, our objective was to characterise a) the abundance and phenotype of cMPs in stable statin-treated heterozygous familial hypercholesterolaemia (FH) patients exposed to life-long hypercholesterolaemia and b) the principal phenotype associated to lipid-rich atherosclerotic plaques in hFH-patients with significant atherosclerotic plaque burden. An age/gender/treatment-matched group of adult-onset non-FH hypercholesterolaemic patients (n=37/group) was comparatively analysed. cMPs were characterised by flow cytometry using annexin-V and cell surface-specific antibodies. Our study shows that LLT-FH patients had higher overall cMP-numbers (p<0.005) than LLT-non-FH patients. Endothelial cell-shed cMPs were also significantly higherin FH (p<0.0005). Within the leukocyte-derived cMP-subpopulations, FH-patients had significantly higher lymphocyte- and monocyte-derived cMP-numbers as well as cMPs carrying leukocyte-activation markers. Normalisation of cMPs by LDL levels did not affect cMP number or phenotype, indicating that the proinflammatory effect was derived from chronic vascular damage. Levels of AV+-total, CD45+-pan-leukocyte and CD45+/CD3+-lymphocyte-derived cMPs were significantly higher in FH-patients with subclinical lipid-rich atherosclerotic plaques than fibrous plaques. Levels of CD45+/CD3+-lymphocyte-MPs above 20,000/ml could differentiate between FH-patients with lipidic or non-lipidic plaques (area under the ROC curve of 0.803, 95%CI: 0.641-0.965, p=0.008). In summary, in this snapshot cross-sectional study cMP concentration and phenotype in FH differed markedly from non-FH hypercholesterolaemia. Patients with life-long high LDL exposure have higher endothelial activation and higher proinflammatory profile, even under current state-of-the-art LLT. cMPs carrying lymphocyte-epitopes appear as markers of lipid-rich atherosclerotic plaques in FH.
We aimed to explore whether changes in circulating levels of miRNAs according to type 2 diabetes mellitus (T2DM) or prediabetes status could be used as biomarkers to evaluate the risk of developing ...the disease. The study included 462 patients without T2DM at baseline from the CORDIOPREV trial. After a median follow-up of 60 months, 107 of the subjects developed T2DM, 30 developed prediabetes, 223 maintained prediabetes and 78 remained disease-free. Plasma levels of four miRNAs related to insulin signaling and beta-cell function were measured by RT-PCR. We analyzed the relationship between miRNAs levels and insulin signaling and release indexes at baseline and after the follow-up period. The risk of developing disease based on tertiles (T1-T2-T3) of baseline miRNAs levels was evaluated by COX analysis. Thus, we observed higher miR-150 and miR-30a-5p and lower miR-15a and miR-375 baseline levels in subjects with T2DM than in disease-free subjects. Patients with high miR-150 and miR-30a-5p baseline levels had lower disposition index (p = 0.047 and p = 0.007, respectively). The higher risk of disease was associated with high levels (T3) of miR-150 and miR-30a-5p (HR
= 4.218 and HR
= 2.527, respectively) and low levels (T1) of miR-15a and miR-375 (HR
= 3.269 and HR
= 1.604, respectively). In conclusion, our study showed that deregulated plasma levels of miR-150, miR-30a-5p, miR-15a, and miR-375 were observed years before the onset of T2DM and pre-DM and could be used to evaluate the risk of developing the disease, which may improve prediction and prevention among individuals at high risk for T2DM.
Colostrum is a nutritious milk synthesized by mammals during the postpartum period, and its rich bioactive components has led to a global increase in the consumption of bovine colostrum as a ...supplement. Bovine colostrum contains key components such as immunoglobulins, oligosaccharides, lactoferrin and lysozyme. It is a special supplement source due to its natural, high bioavailability and high concentrations of growth factors. Growth factors are critical to many physiological functions, and considering its presence in the colostrum, further research must be conducted on its safe application in many bodily disorders. Growth factors contribute to wound healing, muscle and bone development, and supporting growth in children. Additionally, the molecular mechanisms have been explored, highlighting the growth factors roles in cell proliferation, tissue regeneration, and the regulation of immune responses. These findings are crucial for understanding the potential health effects of bovine colostrum, ensuring its safe use, and forming a basis for future clinical applications. This review article examines the growth factors concentration in bovine colostrum, their benefits, clinical studies, and molecular mechanisms.
Scope
It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two ...healthy diets.
Methods and Results
Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. Patients are randomized to a Mediterranean or a low‐fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR:2.56(1.02–6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR:1.94(1.32–2.87) and p = 0.001.
Conclusions
It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease.
A Mediterranean diet reduces serum levels of advanced glycation end products (AGEs) (mainly methylglioxal, MG), reducing dietary AGEs and modulating AGE metabolism. Patients who reduce MG levels after this diet have a higher probability of type 2 diabetes mellitus (T2DM) remission. Serum AGE reduction might be involved in the molecular mechanism underlying diabetes remission of T2DM patients with coronary heart disease.
Ternary quantum dots (QDs) are novel nanomaterials that can be used in chemical analysis due their unique physicochemical and spectroscopic properties. These properties are size-dependent and can be ...adjusted in the synthetic protocol modifying the reaction medium, time, source of heat, and the ligand used for stabilization. In the last decade, several spectroscopic methods have been developed for the analysis of organic and inorganic analytes in biological, drug, environmental, and food samples, in which different sensing schemes have been applied using ternary quantum dots. This review addresses the different synthetic approaches of ternary quantum dots, the sensing mechanisms involved in the analyte detection, and the predominant areas in which these nanomaterials are used.
Evidence from observational and in vitro studies suggests that insulin growth-factor-binding protein type 2 (IGFBP2) is a promising protein in non-communicable diseases, such as obesity, insulin ...resistance, metabolic syndrome, or type 2 diabetes. Accordingly, great efforts have been carried out to explore the role of IGFBP2 in obesity state and insulin-related diseases, which it is typically found decreased. However, the physiological pathways have not been explored yet, and the relevance of IGFBP2 as an important pathway integrator of metabolic disorders is still unknown. Here, we review and discuss the molecular structure of IGFBP2 as the first element of regulating the expression of
. We highlight an update of the association between low serum IGFBP2 and an increased risk of obesity, type 2 diabetes, metabolic syndrome, and low insulin sensitivity. We hypothesize mechanisms of IGFBP2 on the development of obesity and insulin resistance in an insulin-independent manner, which meant that could be evaluated as a therapeutic target. Finally, we cover the most interesting lifestyle modifications that regulate IGFBP2, since lifestyle factors (diet and/or physical activity) are associated with important variations in serum IGFBP2.
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