Clinica e Investigacion en Arteriosclerosis最新文献

{"title":"Telomere length is associated with arterial damage in the CORDIOPREV study","authors":"Ana Ojeda-Rodriguez,&nbsp;Maria Jose Parraga-Viudez,&nbsp;Alejandro López-Moreno,&nbsp;Alejandro Serrán-Jiménez,&nbsp;Alberto Díaz-Cáceres,&nbsp;Javier Arenas-Montes,&nbsp;José D. Torres-Peña,&nbsp;Justo P. Castaño,&nbsp;Javier Delgado-Lista,&nbsp;José López-Miranda","doi":"10.1016/j.arteri.2025.500878","DOIUrl":"10.1016/j.arteri.2025.500878","url":null,"abstract":"<div><h3>Background</h3><div>Telomere length (TL) has emerged as a recognized biomarker of biological aging and cardiovascular risk. Several studies have associated short TL with increased incidence of cardiovascular disease and adverse outcomes. However, its value as a predictor of arterial injury remains unclear, especially in secondary prevention. This study examined the baseline association between TL and common carotid intima-media thickness (IMT-CC) in patients with coronary heart disease (CHD).</div></div><div><h3>Methods</h3><div>Of the 1002 CHD patients enrolled in the CORDIOPREV study, 903 completed baseline assessments of IMT-CC and TL. IMT-CC was measured bilaterally using high-resolution B-mode Doppler ultrasonography and categorized, according to the European Society of Cardiology guidelines, into three groups reflecting arterial injury: &lt;0.7<!--> <!-->mm, 0.7–0.9<!--> <!-->mm, and ≥0.9<!--> <!-->mm. TL was determined using the quantitative PCR method. Patients were classified as at risk of short TL if their value was below the 20th percentile, and as non-risk if above this threshold.</div></div><div><h3>Results</h3><div>Patients with the highest IMT-CC values (≥0.9<!--> <!-->mm) had significantly shorter TL compared to those in the lowest group (&lt;0.7<!--> <!-->mm, <em>p</em> <!-->=<!--> <!-->0.005), with a progressive decrease across IMT-CC categories (<em>p</em> for trend<!--> <!-->=<!--> <!-->0.02). The proportion of participants at risk of short telomeres increased significantly from 15% to 30% across these categories (<em>p</em> <!-->&lt;<!--> <!-->0.001). In addition, the highest IMT-CC group showed a twofold greater risk of short telomeres compared to the reference group (&lt;0.7<!--> <!-->mm; OR 2.373, 95%CI 1.4962–3.764), while no significant association was observed for the intermediate IMT-CC group (0.7–0.9<!--> <!-->mm; OR 1.352, 95%CI 0.896–2.039).</div></div><div><h3>Conclusions</h3><div>In CHD patients, shorter TL is associated to advanced subclinical arterial damage, supporting its potential role as a complementary biomarker for vascular aging and improved risk stratification in secondary prevention.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"38 4","pages":"Article 500878"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670216","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}

{"title":"Electronegative LDL strongly induces LRP1 release from human monocytes and macrophages","authors":"Núria Puig ,&nbsp;Eduardo Garcia ,&nbsp;Montserrat Moncunill ,&nbsp;Aleyda Benítez-Amaro ,&nbsp;Olga Bautista ,&nbsp;Silvia Rodas ,&nbsp;Pol Camps-Renom ,&nbsp;Jose Luis Sanchez Quesada ,&nbsp;Vicenta Llorente-Cortés ,&nbsp;Sonia Benitez","doi":"10.1016/j.arteri.2025.500845","DOIUrl":"10.1016/j.arteri.2025.500845","url":null,"abstract":"<div><h3>Background</h3><div>Electronegative LDL (LDL(−)) is a circulant modified LDL with inflammatory properties whose proportion raises in ischemic events. The soluble form of LDL receptor related protein 1 (sLRP1) increases in blood in pathological situations, including ischemic stroke. We aimed to evaluate the effect of LDL(−) on sLRP1 release from monocytes and macrophages.</div></div><div><h3>Methods</h3><div>LDL(−) and native LDL were isolated from total LDL by anion-exchange chromatography. Both fractions were incubated with THP1 monocytes (overexpressing or not CD14) and derived macrophages. Additional conditions were assayed in macrophages: (1) incubation with aggregated LDLs; (2) LDL fractions in the presence/absence of marimastat, a metalloproteinase inhibitor; and (3) presence/absence of HDL from healthy controls and ischemic stroke patients. After incubation, supernatants and cells were collected for sLRP1 determination by ELISA, and for <em>LRP1</em> expression by real-time PCR, respectively.</div></div><div><h3>Results</h3><div>LDLs promoted sLRP1 release in monocytes and derived macrophages, regardless of CD14 overexpression. The effect was greater for LDL(−), inducing 6-fold and 3-fold higher sLRP1 release in monocytes and macrophages than native LDL. In macrophages, aggregated LDLs induced greater sLRP1 release than their non-aggregated counterparts. The LDL(−)-induced sLRP1 was not induced by promoting <em>LRP1</em> expression or cytotoxicity. Otherwise, inhibition of metalloprotease activity and addition of HDL reduced sLRP1 release. However, HDL from ischemic stroke patients showed an impaired ability to decrease sLRP1 secretion.</div></div><div><h3>Conclusions</h3><div>LDL(−) potently induces sLRP1 in monocytes and macrophages. This action is not mediated by increased <em>LRP1</em> expression, but may be related to the shedding of the membrane form in macrophages.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"38 4","pages":"Article 500845"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034398","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}

{"title":"Atherogenic risk in normal-weight workers: Associations with sociodemographic and healthy lifestyle factors using lipid-based indexes","authors":"Claudia Isabella Tirado Cabrera ,&nbsp;Daniel Guzmán Capote ,&nbsp;Pedro Juan Tárraga López ,&nbsp;Ángel Arturo López-González","doi":"10.1016/j.arteri.2025.500871","DOIUrl":"10.1016/j.arteri.2025.500871","url":null,"abstract":"<div><h3>Background</h3><div>Atherogenic dyslipidemia is a significant but often underrecognized cardiovascular risk factor in individuals with normal weight. Traditional metrics such as body mass index (BMI) may fail to identify metabolically unhealthy phenotypes. This study aimed to assess the prevalence and sociodemographic and lifestyle determinants of atherogenic risk using lipid-based indices in a large cohort of normal-weight Spanish workers.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted in a sample of 166,008 normal-weight workers (BMI 18.5–24.9<!--> <!-->kg/m²). Four atherogenic risk indices were calculated: TC/HDL-c, LDL/HDL-c, TG/HDL-c, and a composite Dyslipidemia Atherogenic Index (DA). Multivariate logistic regression analyses were performed to assess associations with age, sex, educational level, occupational category (CNAE-11), physical activity (IPAQ), adherence to the Mediterranean diet (MEDAS), smoking, and alcohol consumption.</div></div><div><h3>Results</h3><div>Male sex, older age, low physical activity, and poor adherence to the Mediterranean diet were independently associated with elevated values in all four atherogenic indices. The strongest associations were observed for DA with sedentary lifestyle (OR: 9.15; 95% CI: 8.08–10.23) and poor diet quality (OR: 5.23; 95% CI: 4.39–6.07). Notably, 17–22% of normal-weight workers showed abnormal lipid ratios suggestive of increased cardiometabolic risk.</div></div><div><h3>Conclusions</h3><div>Normal BMI does not guarantee cardiometabolic health. A considerable proportion of normal-weight individuals exhibit lipid profiles consistent with atherogenic dyslipidemia, largely driven by modifiable lifestyle factors. Lipid-based indices are valuable tools for early risk identification in occupational settings and should complement traditional anthropometric screening.</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"38 4","pages":"Article 500871"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145349110","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}

{"title":"El ácido bempedoico atenúa la respuesta inflamatoria y el estrés oxidativo vascular en un modelo de aneurisma de aorta abdominal","authors":"Lídia Puertas-Umbert,&nbsp;Judith Alonso,&nbsp;Laia Blanco-Casoliva,&nbsp;Roger Bentanachs,&nbsp;Lluis Asmarats,&nbsp;Gemma Arderiu,&nbsp;José Martínez-González,&nbsp;Cristina Rodríguez","doi":"10.1016/j.arteri.2025.500856","DOIUrl":"10.1016/j.arteri.2025.500856","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation, oxidative stress, and vascular remodeling play a key role in the pathophysiology of abdominal aortic aneurysm (AAA), a severe vascular disease. Previously, we had demonstrated an increase in the phosphorylated form of ATP citrate lyase (p-ACLY) in AAA and that bempedoic acid (BemA), a specific inhibitor of this enzyme, attenuates aneurysm formation in an experimental model. In this study, we further investigated the mechanisms mediating the beneficial effect of BemA.</div></div><div><h3>Methods</h3><div>AAA was induced by angiotensin II (AngII) infusion in ApoE^-/- mice, and aneurysm formation was assessed by ultrasonography. Histological analyses (hematoxylin-eosin, orcein staining) and immunohistochemistry were performed. T cell subpopulations in the spleen were characterized by flow cytometry, and superoxide anion production in the vascular wall was evaluated by dihydroethidium (DHE) staining. The expression of enzymes involved in the control of oxidative stress was analyzed by real-time RT-PCR.</div></div><div><h3>Results</h3><div>Endpoint ultrasonography analyses in AngII-infused ApoE^-/- mice confirmed that BemA limits aneurysm formation. Indeed, BemA administration in AngII-infused mice significantly increased both the percentage of animals that did not develop aneurysms and those free of aortic rupture, without altering the pressor effect of AngII. Histologically, BemA preserved the integrity of the aortic wall and reduced the proportion of animals presenting intramural thrombi, with a decrease in hematoma area. Immunohistochemical analyses showed increased levels of p-ACLY in the inflammatory infiltrate of human and murine aneurysmal lesions, as well as BemA's capacity to attenuate the AngII-induced increase in CD3⁺ T lymphocyte content in the vascular wall. Additionally, analysis of splenic CD8⁺ T cell subpopulations revealed no significant changes in either AngII-infused animals or those treated with BemA. Finally, ACLY activity inhibition decreased reactive oxygen species production without modifying the expression of key isoforms of the NADPH oxidase (<em>Nox2</em>, <em>Nox4</em>) or superoxide dismutase (<em>Sod1</em>, <em>Sod2</em>) families.</div></div><div><h3>Conclusions</h3><div>Taken together, these findings position ACLY as a relevant therapeutic target in AAA and BemA as a drug with potential protective effects against the development and progression of this vascular disease</div></div>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":"38 4","pages":"Article 500856"},"PeriodicalIF":1.9,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145138808","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}

{"title":"Cardiovascular risk and metabolomic profile in adolescents: A comparative study between anorexia nervosa, normal weight, and obesity.","authors":"Jose M Siurana, Neus Martínez-Micaelo, Sara Samino, Cristina Marimon, Rosa Collell, Cristina Girbau, Paula Sol Ventura, Enric Ortigosa, Zelmira Bosch, Nuria Sanz, Anna Sabaté-Rotés, Diego Yeste, Silvia Fernández, Vanessa Sanchez-Gistau, Anna Bonada, Núria Plana, Albert Feliu, Núria Amigó","doi":"10.1016/j.arteri.2026.500955","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500955","url":null,"abstract":"<p><strong>Introduction: </strong>Anorexia nervosa (AN) and obesity represent the extremes of the nutritional spectrum, both being associated with an increase in major adverse cardiovascular events (MACE). The objective of this study was to analyze atherosclerotic risk through the determination of advanced lipoprotein profiling (ALP), fatty acids, and inflammatory markers in adolescents with different weight profiles.</p><p><strong>Methodology: </strong>A cross-sectional study was conducted in 122 adolescents (aged: 10-17 years), divided into three groups based on their Body Mass Index (BMI): underweight/AN (n=47), normal weight (n=33), and moderate-to-severe obesity (n=42). Clinical evaluations, echocardiography to determine structural changes (left ventricular mass index: LVMI) and both conventional and specialized blood analysis using nuclear magnetic resonance spectroscopy (1H-NMR) were performed to quantify ALP, fatty acids, and plasma glycoproteins (GlycA). Multivariate partial least squares-discriminant analysis (PLS-DA) models were employed.</p><p><strong>Results: </strong>The AN group presented with bradycardia, systolic hypotension, and a significant decrease in LVMI, whereas obesity was associated with ventricular hypertrophy and a chronic inflammatory state (elevation of GlycA, leukocytes, and ESR). Although the AN group showed higher total cholesterol and LDL-C levels than the normal-weight group, ALP revealed that this increase is due to larger LDL particle size. Furthermore, subjects with AN exhibited elevated levels of medium HDL particles and cardioprotective fatty acids (omega-3 and DHA). In contrast, the obesity group presented the classic high-risk lipid triad: elevated triglycerides, large VLDL, and small dense LDL. PLS-DA analysis confirmed that BMI is the primary determinant of metabolic and cardiovascular segregation between the groups.</p><p><strong>Conclusions: </strong>Hypercholesterolemia in adolescents with AN constitutes a low-risk physiological adaptation, whereas obesity manifests an early atherogenic profile and adverse cardiac remodeling. Conventional laboratory testing is insufficient to assess real cardiovascular risk in these populations, with ALP proving to be a superior diagnostic tool.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500955"},"PeriodicalIF":1.9,"publicationDate":"2026-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353931","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}

{"title":"Lipid profile and angiogenic markers in the detection of preeclampsia: The RECLAMA study.","authors":"Daiana Ibarretxe, Sara Tameish, Ana González-Lleó, Èrica Cunillera, Natalia Andreychuk, Jara Ballestin, Alba Cabello, Lydia Cabau, Núria Amigó, Carme Grifoll","doi":"10.1016/j.arteri.2026.500946","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500946","url":null,"abstract":"<p><strong>Introduction and objectives: </strong>Preeclampsia (PE) is a multisystem hypertensive disorder affecting 2-8% of pregnancies worldwide and represents a major cause of maternal and fetal morbidity and mortality. Its pathophysiology involves placental dysfunction leading to widespread maternal endothelial injury. Because endothelial damage is closely associated with abnormal lipid metabolism and angiogenic imbalance, the RECLAMA study aims to identify second-trimester biochemical and angiogenic markers associated with PE in a high-risk cohort and to compare them with those observed in a low-risk pregnant population.</p><p><strong>Methods: </strong>In this pilot prospective case-control study, 98 pregnant women were recruited, including high-risk individuals (based on a high-risk result in first-trimester PE screening), women with chronic hypertension, and healthy controls. Clinical data and vascular parameters-carotid intima-media thickness (cIMT), pulse wave velocity (PWV), and augmentation index (AIx)-were collected at gestational week (GW) 14. Serum samples obtained at GW 24 were analyzed for a standard lipid profile, lipoprotein(a) [Lp(a)], and angiogenic factors (sFlt-1, PlGF, and the sFlt-1/PlGF ratio). Results were analyzed according to three patient groups: healthy controls (CG), at-risk patients who did not develop preeclampsia (NoPE), and patients who subsequently developed preeclampsia (PE).</p><p><strong>Results: </strong>Women who subsequently developed PE had a significantly higher prevalence of pre-existing hypertension at baseline (38.46% vs 11.11% and 0% in the NoPE and control groups, respectively; p=0.0089). By the second trimester (GW 24), the PE group had elevated sFlt-1 levels and markedly reduced PlGF concentrations, resulting in a significantly higher sFlt-1/PlGF ratio compared with the NoPE and control groups (p<0.05). Standard lipid parameters show no significant differences, however a trend to higher triglycerides and lower HDL in PE women were observed. In addition, the PE cohort exhibited higher median levels of Lp(a) (37%) at GW 24. At baseline (GW 14), no significant differences were observed among groups in macrovascular markers, including cIMT, PWV, or AIx.</p><p><strong>Conclusions: </strong>In this pilot study, the second-trimester sFlt-1/PlGF ratio was confirmed as a biomarker associated with preeclampsia. Standard lipid parameters show no significant differences, however a trend to proinflammatory atherogenic dyslipidaemia was observed. Moreover, Lp(a) showed a trend toward approximately 37% higher levels in patients who subsequently developed PE, warranting further investigation of this hypothesis-generating observation.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500946"},"PeriodicalIF":1.9,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148309913","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}

{"title":"LDL cholesterol control in patients with atherosclerotic carotid stenosis>50%, previous endarterectomy or carotid stent.","authors":"Lidia Marcos García, Juan Pedro-Botet, Juan Luis Martínez Pérez, Alina Velescu, Carles Diaz Duran, Albert Clarà Velasco","doi":"10.1016/j.arteri.2026.500951","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500951","url":null,"abstract":"<p><strong>Background and aim: </strong>Patients with atherosclerotic carotid disease are at very high cardiovascular risk and often have other vascular territories involved. The main objective of the present study was to assess the degree of LDL cholesterol control in patients with carotid stenosis>50%. Secondary objectives included prescribed lipid-lowering drugs and factors associated with the use of high/very high-intensity lipid-lowering therapy.</p><p><strong>Methods and results: </strong>Consecutive patients who underwent carotid Doppler ultrasound between March 2023 and February 2024 due to a previous endarterectomy or stenting, as well as those with ultrasound findings of stenosis>50%, were included. Clinical, analytical and pharmacological data were collected. LDL-C levels were categorized as <55mg/dL, 55-69mg/dL, and ≥70mg/dL. Multivariable logistic regression was performed to identify factors associated with the use of high- or very high-intensity lipid-lowering therapy. Four hundred patients (mean age 71.7; 77% male) were included. LDL cholesterol<55mg/dL was achieved in 131 (32.8%) of patients. Of the total sample, 259 (64.8%) were on high or very high-intensity therapy. When stratified by LDL-C levels, 32.8% had LDL-C<55mg/dL, 22.2% between 55 and 69mg/dL, and 45.0% ≥70mg/dL. Patients with a concomitant coronary heart disease (n=106, 26.5%) showed a greater rate of LDL cholesterol control (OR=3.1, p<0.001), and those with a history of transient ischemic attack or stroke (OR=1.7, p=0.039 and OR=1.8, p=0.023, respectively), but not those with peripheral arterial disease.</p><p><strong>Conclusion: </strong>In the present study, LDL cholesterol goal was achieved in one in every three patients with atherosclerotic carotid stenosis>50%. Consequently, a substantial residual cardiovascular risk persists in many patients. This gap, and the underuse of high-intensity statin therapy, highlights an important opportunity to improve cardiovascular prevention.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500951"},"PeriodicalIF":1.9,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148260001","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}

{"title":"Lipid lowering therapy in Tangier disease: what is the best association?","authors":"Francesco Sbrana, Beatrice Dal Pino","doi":"10.1016/j.arteri.2026.500954","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500954","url":null,"abstract":"","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500954"},"PeriodicalIF":1.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239781","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}

{"title":"Inclisiran for LDL-C reduction in secondary prevention: Real-world evidence from a homogeneous Spanish cohort with subgroup insights.","authors":"Victoria Piro, Elena Fuente, Francisco Romano, Mario Galván, Miguel Fernández, María Del Val Groba, Marta López, Antonio García","doi":"10.1016/j.arteri.2026.500949","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500949","url":null,"abstract":"<p><strong>Background: </strong>Inclisiran produces sustained LDL-C lowering in clinical trials. Real-world evidence in homogeneous secondary prevention populations is limited.</p><p><strong>Objective: </strong>To evaluate the early effect of inclisiran on LDL-C in a homogeneous secondary prevention cohort with coronary artery disease.</p><p><strong>Methods: </strong>We conducted a retrospective, observational study of 120 adults with established atherosclerotic cardiovascular disease treated with inclisiran between December 2023 and August 2025 at a tertiary care center in Spain. Baseline and 90-day lipid profiles were compared. Subgroup analyses examined LDL-C reduction by sex, type 2 diabetes, statin, ezetimibe, and bempedoic acid use, as well as Lp(a) and remnant cholesterol (RC) levels.</p><p><strong>Results: </strong>Mean baseline LDL-C was 126.1±34.7mg/dL (3.26±0.90mmol/L), decreasing to 45.3±28.3mg/dL (1.17±0.73mmol/L) at 90 days (absolute change -80.9mg/dL; -2.09mmol/L, -63.8%). The therapeutic target, <55mg/dL (<1.4mmol/L), was achieved by 64.5%. Statin users had significantly greater reductions (p<0.01). LDL-C lowering was similar across sexes despite higher baseline levels in women, and slightly greater in patients with diabetes (p=0.48). Elevated Lp(a) showed a weak inverse correlation with LDL-C change although a trend was shown (r=-0.18). RC fell by 16.6% (p=0.008). Bempedoic acid users (n=16) had numerically greater reductions, though not statistically significant probably due to the low n of patients. Inclisiran was well tolerated in this cohort, with no significant adverse events reported.</p><p><strong>Conclusions: </strong>Inclisiran achieved marked LDL-C reductions at 90 days in real-world secondary prevention, especially with the concurrent use of statins. Its twice-yearly dosing and favorable safety profile, in the term observed, support integration into guideline-directed therapy. Larger, longer-term studies should assess durability of effect, long term adherence and the impact on cardiovascular outcomes.</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500949"},"PeriodicalIF":1.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148176977","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}

{"title":"MUC2 promotes cholesterol efflux in foam cells through ALKBH5-mediated m6A modification of ABCA1 mRNA.","authors":"Pingping He, Mao Peng, Yifan Tang, Yuxin Ouyang, Zihang Song, Mi Hu, Xinping Ouyang","doi":"10.1016/j.arteri.2026.500943","DOIUrl":"https://doi.org/10.1016/j.arteri.2026.500943","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerosis (AS) is characterized by lipid accumulation and foam cell formation. Mucin 2 (MUC2), a key intestinal protein, has been linked to lipid metabolism, but its role in atherosclerosis remains unclear. This study aims to elucidate the regulatory mechanism of MUC2 on cholesterol efflux and foam cell formation.</p><p><strong>Methods: </strong>THP-1 macrophage-derived foam cells were treated with MUC2. To investigate the mechanism, cells were transfected with lentiviral vectors for ALKBH5 knockdown (sh-ALKBH5) or overexpression (LV-ALKBH5). Lipid accumulation was assessed by Oil Red O staining and enzymatic cholesterol quantification. Cholesterol efflux was measured using a fluorescence assay. The expression of ABCA1 and ALKBH5 was determined by RT-qPCR and western blotting. M6A modification sites on ABCA1 mRNA were predicted by bioinformatics and verified by MeRIP-MazF assays.</p><p><strong>Results: </strong>MUC2 treatment significantly upregulated ABCA1 expression, promoted cholesterol efflux, and reduced intracellular lipid content in foam cells. Mechanistically, MUC2 inhibited the expression of the m6A demethylase ALKBH5. Consistent with this, MUC2 enhanced the m6A modification level of ABCA1 mRNA. Silencing ALKBH5 mimicked the protective effects of MUC2 by increasing ABCA1 m6A levels and protein expression, thereby facilitating cholesterol efflux. Conversely, ALKBH5 overexpression attenuated the MUC2-induced upregulation of ABCA1 and reversed its protective effects against lipid accumulation.</p><p><strong>Conclusion: </strong>MUC2 promotes cholesterol efflux and inhibits foam cell formation by repressing ALKBH5, which in turn enhances the m6A modification and stability of ABCA1 mRNA. .</p>","PeriodicalId":45230,"journal":{"name":"Clinica e Investigacion en Arteriosclerosis","volume":" ","pages":"500943"},"PeriodicalIF":1.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148164640","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}