👤 Hannah M Rondon Cordero

Lp(a) is a cardiovascular risk factor influenced by the LPA gene and apo(a) isoforms. Their relationship is not always linear and there are discordant phenotypes, for this reason in our work we evaluated the association between apo(a) isoforms and Lp(a) levels in patients with acute coronary syndrome (ACS). To this end, 43 patients with ACS and Lp(a) >50mg/dL were studied. The isoforms were characterized in 12bands by Western blotting. The association between bands and Lp(a) concentrations was evaluated by statistical analysis. It was observed that the intermediate molecular weight bands (b5-b8) were the most frequent, with band 8 predominating. No significant association was found between isoform size and Lp(a) levels (P>.05). We conclude that in this cohort no correlation was observed between apo(a) and Lp(a) isoforms. Other genetic or regulatory mechanisms could explain the observed variability, supporting the need for larger studies. Show less

In recent years we have been experiencing an advance in lipid-lowering therapies, with the appearance of new drugs that act on the different metabolic pathways, reducing both the levels of cholesterol associated with low-density lipoproteins (LDL-C) containing apoproteinB (ApoB), and vascular risk. However, the results in achieving goals are still scarce, as well as the use of the different therapies that help us to achieve them. Among the reasons that justify this situation are: the inadequate identification of vascular risk, the underuse of therapies, poor adherence to the recommended treatment, the lack of organization in terms of the assignment of roles and algorithms of action in the follow-up of patients and the need for improved education and psychosocial interventions that influence both adherence and consolidation of Healthy lifestyle habits. This consensus document aims to improve the approach and follow-up of dyslipidemia in a comprehensive way, defining the planning of lipid-lowering therapies as a control strategy (SEC/SEA/SEEN/SEMFYC/SEMERGEN/SEMG/SEN/SEACV/S.E.N.). Show less

Overexpression of the low-density lipoprotein receptor (LDLR) is known to decrease apolipoprotein E (APOE) levels and alleviate amyloid beta (Aβ) pathology. We hypothesized that inhibiting the Inducible Degrader of LDLR (IDOL), an enzyme that ubiquitinates LDLR for degradation, would increase endogenous LDLR levels and attenuate amyloid pathology. To investigate the cell-type-specific role of IDOL, we generated Idol conditional knockout mice on an Aβ-amyloidosis mouse model and performed biochemical, histological, and multi-omics analyses. We demonstrated that neuronal, but not microglial, Idol deletion reduced amyloid accumulation and altered brain LDLR and APOE levels, indicating the critical role of neuronal IDOL-LDLR in amyloid pathology. In addition, neuronal Idol deletion increased the levels of Reelin receptors important for synaptic function, and single-nuclei RNA sequencing revealed significant changes associated with synaptic organization. Neuronal IDOL, but not microglial IDOL, plays a key role in Alzheimer's disease pathogenesis by regulating the levels of brain APOE receptors. Neuronal, but not microglial, Idol deletion reduces amyloid burden and modulates brain APOE and LDLR levels. Deletion of neuronal Idol increases the levels of APOER2 and VLDLR, the Reelin receptors, in the brain. Single-nuclei RNA sequencing highlights the neuronal IDOL's impact on inhibitory neurons and synaptic organization. Targeting neuronal IDOL may provide multiple therapeutic benefits in Alzheimer's disease by modulating APOE receptors. Show less

Phenotypic heterogeneity is apparent among individuals with putative monogenic disease, such as familial hypertrophic cardiomyopathy. Genome sequencing (GS) allows interrogation of the full spectrum of inborn genetic variation in an individual and RNA profiling provides a snapshot of the cardiac-specific pathogenic effects on gene expression. Identify candidate genetic modifiers of hypertrophic cardiomyopathy phenotype. We performed GS of 48 individuals with variants in GS identified the Evaluation of the whole genome, even in the case of alleged monogenic disease, leads to important new insights. The identified variants, regions, and genes are candidates to modify disease presentation in cardiomyopathy. Show less

Different medical therapies have been developed for pituitary adenomas. However, Non-Functioning Pituitary Neuroendocrine Tumors (NF-PitNET) have shown little response to them. Furthermore, epithelial-mesenchymal transition (EMT) has been linked to resistance to medical treatment in a significant number of tumors, including pituitary adenomas. We aimed to evaluate the expression of EMT-related markers in 72 NF-PitNET and 16 non-tumoral pituitaries. To further explore the potential usefulness of medical treatment for NF-PitNET we assessed the expression of somatostatin receptors and dopamine-associated genes. We found that NF-PitNET showed an enhanced EMT phenomenon. Show less