R. Sarzani, F. Giulietti, M. Allevi, S. Sarnari, Romina Alessandroni, C. di Pentima, F. Spannella
{"title":"Statin-Associated Muscle Symptoms: Clinical Index in a hypertensive population candidated to lipid-lowering therapy but not taking statins","authors":"R. Sarzani, F. Giulietti, M. Allevi, S. Sarnari, Romina Alessandroni, C. di Pentima, F. Spannella","doi":"10.56095/eaj.v2i1.30","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.30","url":null,"abstract":"Aim: Statin-associated muscle symptoms (SAMS) are claimed to be frequent in clinical practice. The SAMS-clinical index (SAMS-CI) assesses the likelihood that muscle symptoms are related to statin use. We evaluated the prevalence and characteristics of muscle symptoms in hypertensive patients eligible for statin therapy according to their individual cardiovascular risk. Methods: Observational study on 390 consecutive outpatients referred to our Centre. All patients were asked the following question: “Have you ever taken a drug/nutraceutical that you think gave you muscle symptoms?”. Patients who answered “yes” were evaluated with SAMS-CI. Results: Mean age: 60.5±13.5 years. Male prevalence: 53.8%. Patients who have ever taken a statin (“statin+” group): 250. Patients who have never taken a statin but have taken at least one other drug (“statin-” group): 140. Prevalence of muscle symptoms did not differ between the groups (p=0.217). Age and number of drugs taken were significantly associated with muscle symptoms at multivariate analysis. A not clinically significant higher SAMS-CI score emerged in the “statin+” group (p=0.004). Localization and pattern of muscle symptoms did not differ between the groups (p=0.170). Timing of muscle symptoms onset after starting the drug (p=0.036) and timing of symptom improvement after withdrawal (p=0.002) were associated with statin therapy. Conclusions: Prevalence of patient-reported muscle symptoms was not associated with statin therapy in our real life clinical study, confirming the growing evidence that subjective muscle-related symptoms are often misattributed to statins, while they may more likely be related to the nocebo/drucebo effect or other common undiagnosed conditions.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114640639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Arca, P. Calabrò, A. Solini, A. Pirillo, R. Gambacurta, K. Ray, A. Catapano, the Santorini Italian Group* the SANTORINI Italian Group*
{"title":"Lipid-lowering treatment and LDL-C goal attainment in high and very high cardiovascular risk patients: Evidence from the SANTORINI study-The Italian experience","authors":"M. Arca, P. Calabrò, A. Solini, A. Pirillo, R. Gambacurta, K. Ray, A. Catapano, the Santorini Italian Group* the SANTORINI Italian Group*","doi":"10.56095/eaj.v2i1.26","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.26","url":null,"abstract":"The SANTORINI study is an observational study that enrolled 9602 adult individuals at high or very high cardiovascular (CV) risk across Europe, aimed at providing information on the current status of the management of dyslipidaemias, in light of the most recent 2019 EAS/ESC guidelines. Italy participated in the study with 1977 patients, 1531 (77.4%) of whom were classified at very high CV risk and 446 (22.6%) at high CV risk. Overall, in the Italian population, 79.31% of the patients had a history of atherosclerotic cardiovascular disease (ASCVD). At enrolment, the mean level of LDL-C in the total population was 98.4 mg/dL. LDL-C levels were lower in the very high-risk group (94.6 mg/dL) than in the high-risk group (111.4 mg/dL). Considering the therapeutic goals recommended by the most recent 2019 ESC/EAS guidelines (LDL-C <55 mg/dL or <70 mg/dL respectively in very high or high-risk patients, respectively), only 20.3% of the overall study population achieved such goals (19.9% of very high-risk patients and 21.8% of high-risk patients). About one-third of the patients included in the study (32.6%) were not prescribed any therapy, one-third received statin monotherapy (34.4%), and only one-third (33%) were taking combination therapy; these percentages were comparable in the two risk subgroups. Based on the most recent 2019 ESC/EAS guidelines, the use of cholesterol-lowering therapies is not always optimal to achieve the therapeutic goals even in patients with very high CV risk. This means that about 80% of patients are far from the recommended therapeutic goals for their risk category.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125483380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Borrelli, N. Marrano, G. Biondi, Martina Rella, Luca Roberto, A. Cignarelli, Sebastio Perrini, L. Laviola, F. Giorgino, A. Natalicchio
{"title":"Irisin administration restores beta-cell functional mass in a mouse model of type 2 diabetes","authors":"Anna Borrelli, N. Marrano, G. Biondi, Martina Rella, Luca Roberto, A. Cignarelli, Sebastio Perrini, L. Laviola, F. Giorgino, A. Natalicchio","doi":"10.56095/eaj.v2i1.45","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.45","url":null,"abstract":"Aim: Irisin is a hormone secreted by skeletal muscle able to improve metabolic homeostasis. Serum irisin levels are reduced in type 2 diabetes (T2D), while exogenous irisin administration improves glycemic control in diabetic mice. We have previously demonstrated that irisin promotes beta-cell survival and function both in vitro and in vivo in healthy wild type mice. We have also demonstrated that irisin restores the defective glucose-stimulated insulin secretion (GSIS) and reduces apoptosis in human pancreatic islets from patients with T2D. Nevertheless, the beta-cellular effects of in vivo irisin administration to T2D mice are still unknown. Methods: C57Bl/6 mice (n = 8) were fed a high-fat diet (HFD, 60% of energy deriving from fat) for 10 weeks and then intraperitoneally injected with streptozotocin (STZ, 100 mg/kg) to induce diabetes. Four standard diet (SD)-fed mice were used as control. HFD/STZ mice were treated with 0.5 μg/g irisin (n = 4) or vehicle (n = 4), for 14 days. Fasting glycemia, insulinemia, body weight, glucose tolerance, and pancreatic islet function were assessed. Pancreatic islet architecture was also evaluated through immunofluorescence analyses. Results: Compared to SD mice, HFD/STZ mice showed higher fasting glycemia and body weight, glucose intolerance, and reduced GSIS; in addition, HFD/STZ mice showed reduced islet volume (-78%), beta-cell area (-35%), and insulin content (-60%), and increased alpha-cell area (+54%). Irisin administration significantly restored glycemia (-31%), body weight (-13%), glucose tolerance (-27%), GSIS (+23%), islet volume (+61%), beta-cell area (+34%) and alpha-cell area (-49%), and insulin content (+36%). Of note, irisin induced a 9-fold increase in beta-cell proliferation rate. Conclusions: These results show that irisin improves glycemic homeostasis and restores the functional beta-cell mass when administered in vivo to diabetic mice, probably by promoting beta-cell proliferation.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130477152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
R. Curcio, Giulia Poli, Consuelo Fabi, Chiara Sugoni, M. Pasticci, Roberto Ferranti, Monica Rossi, I. Folletti, L. Sanesi, Edoardo Santoni, I. Dominioni, M. Cavallo, Giovanni Morgana, Lorenzo Mordeglia, Giovanni Luca, G. Pucci, S. Brancorsini, G. Vaudo
{"title":"Exosomal miRNAs targeting NLRP3 inflammasome platform are associated with radiologic sequelae in survivors of COVID-19-associated acute respiratory distress syndrome","authors":"R. Curcio, Giulia Poli, Consuelo Fabi, Chiara Sugoni, M. Pasticci, Roberto Ferranti, Monica Rossi, I. Folletti, L. Sanesi, Edoardo Santoni, I. Dominioni, M. Cavallo, Giovanni Morgana, Lorenzo Mordeglia, Giovanni Luca, G. Pucci, S. Brancorsini, G. Vaudo","doi":"10.56095/eaj.v2i1.35","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.35","url":null,"abstract":"Background: There is limited understanding of the pathophysiology of post-acute pulmonary sequelae in COVID-19-associated acute respiratory distress syndrome (ARDS). We aimed at investigating the association of circulating microRNAs (miRNAs) involved in post-transcriptional regulation of NLRP3-inflammasome pathways and lung radiological features among COVID-19- associated ARDS survivors. Methods: We evaluated COVID-19-associated ARDS survivors at 4±2 months from clinical recovery. Patients were selected based on imaging pattern evolution according to chest high-resolution computerized tomography (HRCT) findings into “fully recovered” (FR), “pulmonary opacities” (PO) and “fibrosis-like lesions” (FL) according to radiological appearance. Plasma miRNA profiling was performed using real time quantitative polymerase chain reaction (RT-qPCR). The exosomal expression of NLRP3 inflammasome related miRNAs (miR-17-5p, miR-223-3p, miR-146a-5p) was evaluated. Results: 31 patients (33% men, mean age 60±6 years, mean BMI 31.1±6.6 Kg/m2) were selected for the present study. No statistically significant differences between FR, PO and FL patterns were observed according to clinical features. NLRP3-inflammasome-related miRNAs such as miR-17-5p, miR-223-3p and miR-146a-5p were significantly up-regulated in patients with PO when compared to patients with FL. miR-146a-5p was also up-regulated in patients with FL than in FR. Conclusions: In patients with long-term pulmonary radiological sequelae following COVID71 19- associated ARDS, a down-regulation of miRNAs inhibiting NLRP3 (miR-17-5p, miR-146a72 3p and miR-223-3p) correlated to fibrosis development in patients showing persistent hyper-reactivity to inflammatory stimulation. NLRP3-Inflammasome-related miRNAs could be a possible therapeutic target to prevent the fibrotic evolution of COVID-19-associated ARDS.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133795079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Airale, Simona Votta, Anna Colomba, G. Mingrone, Arianna Paladino, A. Astarita, M. Cesareo, C. Catarinella, Francesca Novello, A. Milan
{"title":"How age and gender affect hemodynamic forces in healthy subjects","authors":"L. Airale, Simona Votta, Anna Colomba, G. Mingrone, Arianna Paladino, A. Astarita, M. Cesareo, C. Catarinella, Francesca Novello, A. Milan","doi":"10.56095/eaj.v2i1.29","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.29","url":null,"abstract":"Aim: noninvasive echocardiographic analysis of blood-tissue interaction has recently been made possible by a sophisticated mathematical model. This model uses speckle-tracking technology to estimate instantaneous intraventricular gradients (IVPGs), which are represented as hemodynamic forces (HDFs). The aim of the present study is to examine how HDFs are affected by gender and age, providing reference value. Methods: 85 healthy subjects were recruited and underwent transthoracic echocardiography. Speckle-tracking analysis was performed from the three apical views, and the mitral annulus and left ventricular outflow tract were measured to compute HDFs. Longitudinal HDFs have been examined, decomposing them in amplitude and time parameters. Results: study population showed a median age of 47[25-60] years and 53% were female. Female patients showed lower LVMi (60.1±11.8mg/m2 vs. 71.4±16.8mg/m2, p=0.001), lower LVEDV (84.6±14.6ml vs. 108±20.7ml, p<0.001), and a lower E/e’ (7.26[6.47;7.78] vs. 5.31 [4.77;6.30], p<0.001). Nor systolic nor diastolic blood pressure differed between male and female patients (p NS for both). Several time parameters differed between gender: female subjects had a later systolic deceleration peak (38.7±4.21% vs. 34.8±4.31%, p<0.001) and a later diastolic deceleration peak (60.9±7.64% vs. 56.5±8.39%, p=0.015). No amplitude HDFs parameter was found to differ between gender (p NS for all). Regarding age, patients over50 years showed higher systolic (124±15.4mmHg vs. 115±10.8mmHg, p=0.008) and diastolic (75.2±8.99mmHg vs. 69.8±7.16mmHg, p=0.005) blood pressure, and higher E/e’ (7.41[6.91;8.58] vs. 5.58[4.81;6.56], p<0.001). HDFs time variables differed between patients under and over50 years: systolic ejection duration was longer in over50-group (27.8±3.44% vs. 25.6±3.48%, p=0.005), systolic deceleration duration was shorter in over50-group (7.69±1.48% vs. 8.54±1.97%, p=0.025) and systolic acceleration peak was earlier in over50-group (13.5±2.46% vs. 14.8±2.59%, p=0.020). Conclusion: Among healthy subjects, female patients showed later systolic deceleration peak and later diastolic deceleration peak. Subjects over50 years showed longer systolic ejection duration, shorter systolic deceleration duration and earlier systolic acceleration peak.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"49 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127412931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Tramontano, S. Bini, A. Di Costanzo, I. Minicocci, S. Covino, M. Arca, L. D’Erasmo
{"title":"Thrombocytopenia and Kidney disease, two possible hallmark of FCS phenotype: preliminary evidence from a cohort study","authors":"D. Tramontano, S. Bini, A. Di Costanzo, I. Minicocci, S. Covino, M. Arca, L. D’Erasmo","doi":"10.56095/eaj.v2i1.42","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.42","url":null,"abstract":"Background and Aim: Familial Chylomicronemia Syndrome (FCS) is a rare monogenic autosomal recessive disorder of lipid metabolism determining severe hypertriglyceridemia (HTG). As the use of Volanesorsen, a novel FCS treating drug, has been associated with thrombocytopenia, the relationship between FCS and low platelets counts should be firmly established. It has been reported also kidney complication in FCS, but the data are sparse. To this aim, we have retrospectively evaluated the spontaneous variation of platelet counts and Kidney impairment in a cohort of patients with FCS. Methods: Single-center retrospective cohort study on 20 FCS patients included in the LIPIGEN. Medical charts have been revised to collect retrospectively information on kidney function in a cohort of patients with FCS. Results: Across the study population, the median PLT count was 187,225 platelet/mcL. The median on treatment TG levels in the whole cohort was 1309 mg/dl. During follow-up, 8 (44.4%) patients experienced at least one episode of mild and 1 (5%) of moderate thrombocytopenia. None had severe thrombocytopenia. Mean triglycerides do not significantly predict mean platelet values. However, when considering a multivariate model including mean triglycerides, sex, the presence of hepatic steatosis and age we found that male sex and the presence of ultrasound estimated hepatic steatosis were associated with significantly lower platelet (respectively β-0,473, P=0,044 and β-0,469, P=0,048). Age was of borderline statistical significance (β-0,388, P=0,087). Across the study population, the median GFR values was 99.5 ml/min. Median eGFR was significantly associated with history of hypertension (β-0,508, P=0,031). Overall, proteinuria occurred in 5 (25%) patients, and it did not associate with hypertension, diabetes, age, sex nor triglyceride levels. Four (20.0%) patients meet the criteria of hyperfiltration whereas 3 (15.0%) were exhibiting an eGFR below 90 ml/min. Among hyperfiltrating, two had also proteinuria in at least one occasion during life. One patient with eGFR below 90 ml/min and proteinuria had a biopsy-proven diagnosis of glomerulonephritis. Overall, the impairment in kidney function was independent from age, diabetes, hypertension, median TGs, AP, sex. Conclusions: The present analysis confirmed that thrombocytopenia and kidney impairment might be a clinical characteristics of FCS phenotype. Further studies in larger cohort are needed to better clarify if kidney disease and thrombocytopenia might be a hallmark of FCS in broader population and understand the potential patho-physiological mechanism.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125987642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
F. Bonacina, J. Nour, A. Moregola, Gianluigi Inzoli, O. Terenghi, Francesca Fantini, G. Norata
{"title":"Impact of immune system humanization on atherosclerosis in dyslipidemic Rag2-KO/IL2rg-KO/CD47-KO/LDL-R KO mice","authors":"F. Bonacina, J. Nour, A. Moregola, Gianluigi Inzoli, O. Terenghi, Francesca Fantini, G. Norata","doi":"10.56095/eaj.v2i1.38","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.38","url":null,"abstract":"Aim: Given the key role of the immune response during atherosclerosis and the therapeutic interest of biologics targeting human immune cells, the need of experimental models to translate molecular mechanisms and to test therapeutic approaches for atherosclerosis is continuously increasing. Here we describe the characteristics of an innovative immunodeficient mouse humanized with hCD34+ cells on an atheroprone background. Methods: LDLR-KO mice were crossed with the immunodeficient C57BL/6J strain Rag2-KO/IL2rg-KO/CD47-KO (TKO, IMSR_JAX:025730) to generate an immunocompromised dyslipidemic mouse TKO-LDLR KO recipient of human hematopoietic stem cells (hCD34+). Results: TKO-LDLR KO were first characterized for their immune and metabolic profile. TKO mice are deficient in mature lymphocytes and NK cells and this profile was conserved in TKO-LDLR KO mice. Under high cholesterol diet for 8 weeks, both males and females TKO-LDLR KO present monocytosis with increased levels of Ly6Chi monocytes compared to TKO-LDLR KO at standard diet, develop marked dyslipidemia (total cholesterol 870.9 and 890.1 mg/dL male and females respectively), steatosis and atherosclerosis. This profile confirms the suitability of TKO-LDLR KO mice for atherosclerosis studies. Next, we tested the impact of immune system humanization. TKO-LDLR KO pups received a low-dose irradiation (150-200 cGy) and thereafter 1,5-2 x 10^5 hCD34+ were injected with in the liver. Engraftment of human leukocytes (hCD45+) was evaluated after two months by flow cytometry analysis from tail blood. This approach allows to reconstitute between 10-30% of hCD45+, mainly B and T cells. Conclusions: We have generated and characterized for the first time a humanized dyslipidemic TKO-LDLR KO mouse. This mouse model presents human B and T cells and could represent an important tool to investigate the impact of biologics targeted toward human targets in the context of atherosclerosis.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"90 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124238433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Cavicchioli, S. Lugari, Michela D’Avino, F. Carubbi, F. Nascimbeni
{"title":"Successful treatment with lomitapide in a patient with homozygous familial hypercholesterolemia and severe fatty liver disease","authors":"A. Cavicchioli, S. Lugari, Michela D’Avino, F. Carubbi, F. Nascimbeni","doi":"10.56095/eaj.v2i1.33","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.33","url":null,"abstract":"Introduction and Aims: Homozygous-familial hypercholesterolemia (Ho-FH) is a rare condition due to biallelic mutations in low-density lipoprotein-receptor (LDL-R) genes characterized by high level of LDL-cholesterol (LDL-c) and huge risk of premature atherosclerotic cardiovascular disease (ASCVD), determining low quality of life and life expectancy. Lomitapide represents a therapeutic option for Ho-FH, but caution should be observed when used in fatty liver disease (FLD) and hypertransaminasemia since it is associated with onset/worsening of liver steatosis. We present a case of safe lomitapide therapy in an adult Ho-FH patient with pre-existing FLD. Case presentation: A 39-year-old man with severe hypercholesterolemia since childhood (LDL-c 405 mg/dl) and premature coronary heart disease history, was referred to our Modena Lipid Clinic. He presented an overt metabolic syndrome, FLD with hypertransaminasemia and elastosonographic significant liver fibrosis. Lipid-lowering-therapy (LLT) included rosuvastatin 20 mg, ezetimibe and evolocumab 140 mg twice a month without reaching LDL-c goal. Genetic analysis revealed homozygous pathogenic LDL-R gene mutation. Evolocumab was increased up to 420 mg twice a month and LDL-apheresis was started with quality of life worsening. Therefore, lomitapide 5 mg daily and low-fat diet were started, obtaining weight loss and lipid profile improvement. However, liver enzymes elevation higher than 5-fold was observed, leading to lomitapide discontinuation and baseline liver enzymes values restoration. After one-month wash-out, lomitapide was gradually reintroduced up to 5 mg daily without significant hypertransaminasemia recurrence, leading to LDL-c target achievement and LDL-apheresis discontinuation. Adherence to low-fat diet and weight loss resulted in FLD and fibrosis improvement. Conclusion: Ho-FH requires complex, combined treatment. Metabolic comorbidities co-existence makes Ho-FH management more difficult. Lomitapide can be safely used in Ho-FH patients with FLD and hypertransaminasemia, but strict follow-up of liver disease and a multidisciplinary approach are needed. Before lomitapide introduction, low-fat diet should be started advantageously and weight stabilization should be obtained.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132154342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Svecla, A. Moregola, L. Da Dalt, J. Nour, A. Baragetti, P. Uboldi, Fabeizia Bonacina, G. Norata
{"title":"Role of ASGR1 on obesity and metabolic syndrome","authors":"M. Svecla, A. Moregola, L. Da Dalt, J. Nour, A. Baragetti, P. Uboldi, Fabeizia Bonacina, G. Norata","doi":"10.56095/eaj.v2i1.39","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.39","url":null,"abstract":"Background: Obesity-related fat accumulation is linked to the metabolic syndrome and increases the risk of CVD by involving FFA, insulin resistance, and inflammation. Taking into account the findings from the third chapter, our goal was to assess the potential role of ASGR1 in metabolic reprogramming and immunoinflammatory state during obesity. Methods: After 20 weeks of high fat diet, flow cytometry, proteomics, lipid profile, glucose tolerance, and insulin tolerance were assessed in WT and ASGR1-/- mice (HFD). Additionally, metabolic parameters such as oxygen consumption, CO2 production, and food intake were measured during the diet. Results: After 20 weeks of HFD, the ASGR1−/− mice displayed a significant reduction in the circulating monocytes compared to WT. The body weight and food intake were comparable in between two groups. The adipose tissue VAT was significantly increased in ASGR1-/- compared to WT mice (WT 3.2%±0.8%, ASGR1-/- 4.7%±1.2%, P-value<0.001). The proteomics revealed, n=3412 proteins were aligned from which 624 proteins were significantly differentially expressed on the liver of ASGR1-/- and WT mice under HFD. From prediction analysis the significant proteins that were increase in the liver of ASGR1-/- mice were necrosis, apoptosis, and inflammation compared to the WT. Additionally, a significant downregulation in proteins protein expression involved in fatty acid synthesis and fatty acid uptake, except the increased expression of fatty acid coenzyme A ligase (FATP5), which belongs to very long chain acyl-CoA synthetases, capable mediation the transport of long chain fatty acids. Conclusion: Our findings indicate that ASGR1 deficiency causes increased inflammation and changes in metabolic pathways when subjected to HFD. This can also have an impact on the synthesis of apolipoproteins secreted in plasma.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"3 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133095290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Pavanello, Vanessa Bianconi, L. Da Dalt, G. Gallo, C. Mancusi, M. Ciccarelli, A. Maloberti, F. Spannella, F. Fimiani, D. D’Ardes, R. Lombardi, G. Talerico, Massimiliano Cavallo
{"title":"Spring Meeting of the Young Researchers of SID, SIIA, SIMI, SIPREC, SISA","authors":"C. Pavanello, Vanessa Bianconi, L. Da Dalt, G. Gallo, C. Mancusi, M. Ciccarelli, A. Maloberti, F. Spannella, F. Fimiani, D. D’Ardes, R. Lombardi, G. Talerico, Massimiliano Cavallo","doi":"10.56095/eaj.v2i1.28","DOIUrl":"https://doi.org/10.56095/eaj.v2i1.28","url":null,"abstract":"The VIII Spring Meeting of Young Researchers of the Italian Society of Diabetology (SID), the Italian Society of Arterial Hypertension (SIIA), the Italian Society of Internal Medicine (SIMI), the Italian Society of Cardiovascular Prevention (SIPREC) and the Italian Society for the Study of Atherosclerosis (SISA) “Basic and clinical research: Until grant let us apart” was held in Rimini on April 16-18, 2023. As is customary, the Congress was organized by the young members of the aforementioned scientific societies operating in the cardiometabolic field. The Congress featured five sessions dedicated to the discussion of the recent evidence from both basic and clinical researchers in cardiometabolic treatment and prevention. Many young researchers had the opportunity to present their scientific works in dedicated oral and poster sessions. In this report, we provided a summary of the main issues discussed during the Meeting lectures.","PeriodicalId":227903,"journal":{"name":"European Atherosclerosis Journal","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124503479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}