Gabriela Berg

Objective: This study aimed to evaluate the clinical and functional impact of a novel apolipoprotein A5 (ApoA5) variant by assessing lipoprotein lipase (LPL) activity. Subjects and methods: Demographic and clinical data, including blood lipid levels and body mass index, were retrospectively collected from an endocrinology clinic registry. Ten individuals with familial chylomicronemia syndrome (FCS) carrying a novel APOA5 variant were included. Whole-exome sequencing was performed using the latest generation DNB-SEQ400 platform. LPL activity was measured in post-heparin plasma using a radiometric assay. Statistical analysis: Categorical variables were summarized as frequencies and percentages, and continuous variables as mean ± standard deviation or median (range), as appropriate. Group comparisons were performed using the Mann-Whitney U test or chi-square test. Analyses were conducted using the Statistical Package for the Social Sciences software (v. 25.0). A p-value < 0.05 was considered statistically significant. Results: We report ten cases of FCS with a homozygous missense variant of uncertain significance in APOA5: c.694T>C; p.(Ser232Pro), located in exon 3. In six patients assessed for LPL activity, levels remained consistently below 20% compared to normotriglyceridemic controls. The addition of exogenous serum containing APOA5 restored LPL activity to above 20% in all cases, indicating functional rescue. Conclusion: Measurement of LPL activity demonstrated the functional impact of the APOA5 c.694T>C; p.(Ser232Pro) variant. These findings support reclassification of the variant as likely pathogenic and enable differentiation from multifactorial chylomicronemia syndrome.

Background/Objectives: Ischemic postconditioning (IP) is a well-established intervention that mitigates this damage by activating endogenous cardioprotective pathways. However, the presence of comorbidities such as dyslipidemia can disrupt these protective mechanisms and abolish the infarct-sparing effect typically induced by IP. In this context, identifying pharmacological strategies to restore cardioprotection is of clinical relevance. This study aimed to evaluate whether N-acetylcysteine (NAC), a glutathione precursor with antioxidant properties, can restore the infarct-limiting effect of IP compromised by HFD-induced oxidative stress. Methods: Male mice were fed a control diet (CD) or HFD for 12 weeks. NAC (10 mM) was administered in drinking water for 3 weeks before ex vivo myocardial ischemia/reperfusion (I/R) injury (30 min ischemia/60 min reperfusion). In IP groups, six cycles of brief I/R were applied at the onset of reperfusion. Infarct size, ventricular function, redox status (GSH/GSSG), lipid profile, and histology were evaluated. Results: NAC improved the lipid profile (HDL/non-HDL ratio) and enhanced the infarct-sparing effect of IP in CD-fed mice. In HFD-fed mice, NAC restored the efficacy of IP, significantly reducing infarct size (HFD-I/R-NAC: 39.7 ± 4.5% vs. HFD-IP-NAC: 26.4 ± 2.0%, p < 0.05) without changes in ventricular function. The ratio of oxidized/reduced glutathione (GSSG/GSH) is depicted. Under basal conditions, the hearts of mice fed an HFD exhibited a shift towards a more oxidized state compared to the control diet CD group. In the I/R protocol, a significant shift towards a more oxidized state was observed in both CD and HFD-fed animals. In the IP protocol, the GSSG/GSH ratio revealed a tendency to basal values in comparison to the I/R protocol. The analysis indicates that animals subjected to I/R and IP protocols in conjunction with NAC show a tendency to reach basal values, thus suggesting a potential for the reduction in ROS. Conclusions: NAC treatment mitigates oxidative stress and restores the cardioprotective effect of ischemic postconditioning in a model of early-stage atherosclerosis. These findings support NAC as a potential adjunct therapy to improve myocardial resistance to reperfusion injury under dyslipidemic conditions

El tejido adiposo epicardico (TAE) es un tejido metabólicamente activo que ha cobrado gran interés en la última década como marcador de riesgo cardiovascular. El TAE se relaciona con la producción de citoquinas proinflamatorias y de ácidos grasos libres, con la promoción de un estado de hipercoagulabilidad, y con numerosos factores de riesgo cardiometabólico. Existe una íntima relación entre las arterias coronarias y el TAE, no solo anatómica, sino en cuanto a aspectos fisiológicos bidireccionales de regulación paracrina. Además, numerosos estudios han encontrado una relación entre el TAE y la presencia de disfunción endotelial, ateromatosis no obstructiva, estrés oxidativo, fibrilación auricular, y disfunción diastólica.En paralelo, existe una estrecha relación entre la esteatosis hepática (la enfermedad hepática crónica más frecuente), la ateromatosis coronaria, y el riesgo cardiovascular. Una de las características interesantes de la esteatosis hepática y diferenciales con respecto a la enfermedad coronaria es su carácter dinámico y, en cierta medida, reversible. A pesar de las asociaciones descriptas con la ateromatosis y con el riesgo cardiovascular, y de su evaluación sencilla a partir de métodos de imagen no invasivos, la grasa epicárdica y el hígado graso no alcohólico son raramente considerados como marcadores de riesgo en la práctica clínica.

Introduction: Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder that affects approximately 1 to 10 individuals per million and is caused by variants in the genes encoding for the lipoprotein lipase (LPL) enzyme. In addition to its heterogeneous clinical presentation, FCS is characterized by a higher risk of life-threatening, recurrent acute pancreatitis and type 3 diabetes. Since available evidence on FCS in Latin America is limited, there is a clear need for a consensus document that provides relevant [...] Abstract Introduction: Familial chylomicronemia syndrome (FCS) is an autosomal recessive disorder that affects approximately 1 to 10 individuals per million and is caused by variants in the genes encoding for the lipoprotein lipase (LPL) enzyme. In addition to its heterogeneous clinical presentation, FCS is characterized by a higher risk of life-threatening, recurrent acute pancreatitis and type 3 diabetes. Since available evidence on FCS in Latin America is limited, there is a clear need for a consensus document that provides relevant