Atherosclerosis plus最新文献

{"title":"Low HDL-c levels at admission are associated with greater severity and worse clinical outcomes in patients with COVID-19 disease","authors":"Sandra Parra ,&nbsp;Mireia Saballs ,&nbsp;Mark DiNubile ,&nbsp;Mireia Feliu ,&nbsp;Simona Iftimie ,&nbsp;Laia Revuelta ,&nbsp;Raul Pavón ,&nbsp;Alba Àvila ,&nbsp;Susan Levinson ,&nbsp;Antoni Castro","doi":"10.1016/j.athplu.2023.01.002","DOIUrl":"10.1016/j.athplu.2023.01.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>HDL particles may act to buffer host cells from excessive inflammatory mediators. The aim of this study is to investigate if the lipid profile provides a prognostic biomarker for COVID-19 outcomes.</p></div><div><h3>Methods</h3><p>This was a prospective study of the characteristics of 125 adult COVID-19 patients with a lipid profile performed on the day of admission analyzed with regard to clinical outcomes.</p></div><div><h3>Results</h3><p>Seventy-seven patients (61.2%) were men, with a mean age of 66.3 (15.6) years. 54.1% had bilateral pneumonia. The all-cause mortality rate during hospitalization was 20.8%. We found a direct association between more severe disease assessed by the WHO classification, admission to the ICU and death with more pronounced lymphopenia, higher levels of CRP, ferritin (<em>p</em> &lt; 0.001), D-dímer and lactate dehydrogenase (LDH) all statistically significant. Lower leves of HDL-c and LDL-c were also associated with a worse WHO classification, ICU admission, and death,. HDL-c levels were inversely correlated with inflammatory markers CRP (<em>r</em> = −0.333; <em>p</em> &lt; 0.001), ferritin (<em>r</em> = −0.354; <em>p</em> &lt; 0.001), D-dímer (<em>r</em> = −0.214; <em>p</em> &lt; 0.001), LDH (<em>r</em> = −0.209; <em>p</em> &lt; 0.001. LDL-c levels were significantly associated with CRP (<em>r</em> = −0.320; <em>p</em> &lt; 0.001) and LDH (<em>r</em> = −0.269; <em>p</em> &lt; 0.001). ROC curves showed that HDL [AUC = 0.737(0.586–0.887), <em>p</em> = 0.005] and lymphocytes [AUC = 0.672(0.497–0.847], <em>p</em> &lt; 0.043] had the best prognostic accuracy to predict death. In a multivariate analysis, HDL-c (β = −0.146(0.770–0.971), <em>p</em> = 0.014) and urea (β = 0.029(1.003–1.057), <em>p</em> = 0.027) predicted mortality.</p></div><div><h3>Conclusion</h3><p>Hypolipidemia including HDL levels at admission identifies patients with a higher risk of death and worse clinical manifestations who may require more intensive care.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"52 ","pages":"Pages 1-8"},"PeriodicalIF":1.6,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9988188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9096496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Young women with familial hypercholesterolemia have higher LDL-cholesterol burden than men: Novel data using repeated measurements during 12-years follow-up","authors":"Anja K. Johansen ,&nbsp;Martin P. Bogsrud ,&nbsp;Jacob J. Christensen ,&nbsp;Amanda Rundblad ,&nbsp;Ingunn Narverud ,&nbsp;Stine Ulven ,&nbsp;Gisle Langslet ,&nbsp;Kjetil Retterstøl ,&nbsp;Kirsten B. Holven","doi":"10.1016/j.athplu.2023.01.001","DOIUrl":"10.1016/j.athplu.2023.01.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>The concentration and the duration of exposure to low-density lipoprotein cholesterol (LDL-C) (LDL-C burden) is an important determinant of risk for cardiovascular disease and thresholds has recently been estimated. Individuals with familial hypercholesterolemia (FH) have increased risk of premature cardiovascular disease. The overall aim of the present study was to describe differences in LDL-C level and LDL-C burden in females and males with FH visiting an outpatient lipid clinic from a young age, using multiple LDL-C measurements during a follow-up time of 12 years. First, we aimed to study if the LDL-C concentration and the LDL-C burden is different between females and males at ages 0–10, 10–20, 20–30 and &gt;30 years. Second, we aimed to estimate the subject-specific LDL-C burden at age 19 and 30 years, and the proportion of female and male patients that reach suggested LDL-C thresholds indicating high risk of ASCVD.</p></div><div><h3>Methods</h3><p>Data was retrospectively collected from medical records of 438 subjects (207 girls and 231 boys) with FH, referred to the Lipid Clinic, Oslo University Hospital below the age of 19 years. The LDL-C burden was estimated based on repeated LDL-C measurements over time.</p></div><div><h3>Results</h3><p>Subjects were followed over a period of mean 12.0 (SD 7.0) years, with median 10 years (7–17; 25–75 percentiles, minimum 2), with median 6 (4–9; 25–75 percentiles, minimum 2) available LDL-C measurements, starting at mean age 11 (SD 3.9) years. There was a difference in both LDL-C and LDL-C burden between sexes at different ages. On average, males had lower LDL-C over time, although this difference was less pronounced with age and males also had lower estimated LDL-C burden over time, and this difference was further exacerbated with age.</p></div><div><h3>Conclusion</h3><p>Our study shows that young women with FH have a higher LDL-C burden than their male counterparts, potentially explaining the increased excess CVD risk seen among these. It underscores the importance of careful-follow up and early treatment initiation both prior to and after pregnancies in order to limit statin-free periods.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"51 ","pages":"Pages 28-34"},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9995918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9455819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of urinary isoprostanes with measures of subclinical atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA)","authors":"Ryan L. Wallace ,&nbsp;Oluseye Ogunmoroti ,&nbsp;Di Zhao ,&nbsp;Dhananjay Vaidya ,&nbsp;Amir Heravi ,&nbsp;Eliseo Guallar ,&nbsp;Chiadi E. Ndumele ,&nbsp;Joao A.C. Lima ,&nbsp;Pamela Ouyang ,&nbsp;Matthew J. Budoff ,&nbsp;Matthew Allison ,&nbsp;Isac Thomas ,&nbsp;Oluwaseun E. Fashanu ,&nbsp;Ron Hoogeveen ,&nbsp;Wendy S. Post ,&nbsp;Erin D. Michos","doi":"10.1016/j.athplu.2022.12.002","DOIUrl":"10.1016/j.athplu.2022.12.002","url":null,"abstract":"<div><h3>Background</h3><p>Urinary isoprostanes are markers of systemic oxidative stress, which is implicated in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD). Coronary artery calcium (CAC), thoracic aortic calcium (TAC) and carotid plaque are measure subclinical atherosclerosis and prognosticate ASCVD risk. We examined the associations between urinary isoprostane levels and measures of plaque prevalence, burden, incidence and progression across three vascular beds in a cohort from the Multi-Ethnic Study of Atherosclerosis.</p></div><div><h3>Methods</h3><p>Urinary levels of 8-isoprostane and 2,3-dinor-8-F₂-isoprostane were measured in 1089 participants (mean ± SD 62 ± 8 years, 48% women) at baseline. Participants underwent computed tomography for CAC and TAC, and duplex ultrasound for carotid plaque. TAC and CAC were reassessed at 2.4 and 10 years, respectively. Regression models were adjusted for CVD risk factors.</p></div><div><h3>Results</h3><p>In adjusted models, there were no significant associations between isoprostane levels with CAC prevalence or progression. Highest versus lowest tertile of 8-isoprostane was associated with 28% lower prevalence of descending TAC at baseline [prevalence ratio (PR) 0.72 95% CI (0.56, 0.94)], while 1-SD higher 2,3-dinor-8-F₂-isoprostane was associated with 96% higher incident ascending TAC at follow-up [Relative Risk 1.96 (1.24, 3.09)]. Highest versus lowest tertile of isoprostane measures were associated with 22% higher prevalence of carotid plaque [(PR 1.22 (1.04, 1.45)] and 14% difference [3,26] in greater extent of carotid plaque at baseline.</p></div><div><h3>Conclusions</h3><p>Higher urinary isoprostanes were inconsistently associated with some measures of subclinical atherosclerosis by imaging. This suggests a limited role of urinary isoprostane levels as a prognostic marker for the development of ASCVD.</p></div><div><h3>Trial registration</h3><p>The MESA cohort design is registered at <span>clinicaltrials.gov</span><svg><path></path></svg> as follows: <span>https://clinicaltrials.gov/ct2/show/NCT00005487</span><svg><path></path></svg>.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"51 ","pages":"Pages 13-21"},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dyslipidemia and the preventive potential in the Greenlandic population","authors":"Johan Skov Bundgaard ,&nbsp;Marit E. Jørgensen ,&nbsp;Kristine Andersen ,&nbsp;Henning Bundgaard ,&nbsp;Uka Wilhjelm Geisler ,&nbsp;Michael Lynge Pedersen","doi":"10.1016/j.athplu.2022.12.003","DOIUrl":"10.1016/j.athplu.2022.12.003","url":null,"abstract":"<div><h3>Background</h3><p>Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for development of cardiovascular diseases. Based on available clinical data, we aimed to investigate the plasma lipid profile in the Greenlandic population, the proportion on cholesterol-lowering treatment and the adherence to local indications for cholesterol-lowering therapy.</p></div><div><h3>Methods</h3><p>This is an observational cross-sectional study of the adult (≥21 years) Greenlandic population with focus on clinically determined lipid levels from 2017 to early 2022. We investigated levels of dyslipidemia and assessed cholesterol-lowering medication usage in individuals with an indication according to current Greenlandic guidelines, which include a) LDL-C &gt;5 mmol/l, b) diabetes, c) diagnosed atherosclerotic disease and 4) a SCORE2 &gt;7.5%.</p></div><div><h3>Results</h3><p>In the adult Greenlandic population of 40,565 individuals a lipid profile was available in 13,895 with a mean LDL-C of 3.0 mmol/L and 976 (7%) had a LDL-C &gt;5 mmol/l. One or more indications for cholesterol-lowering medication was present in 3988 individuals and a total of 5464 adult Greenlanders either fulfilled local criteria for statin therapy or received a statin (some without current indication) and among these, 2232 (41%) individuals received no statin.</p></div><div><h3>Conclusion</h3><p>These findings indicate that clinically significant dyslipidemia is common in the adult Greenlandic population and that the cardiovascular preventive potential of cholesterol-lowering therapy is currently underutilized.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"51 ","pages":"Pages 22-27"},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037086/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lp(a) does not affect intima media thickness in hypercholesterolemic children –a retrospective cross sectional study","authors":"Oliver Helk ,&nbsp;Andreas Böck ,&nbsp;Claudia Stefanutti ,&nbsp;Kurt Widhalm","doi":"10.1016/j.athplu.2022.11.001","DOIUrl":"10.1016/j.athplu.2022.11.001","url":null,"abstract":"<div><h3>Purpose</h3><p>Combined hyperlipidaemia results in premature atherosclerosis and a high burden of cardiovascular morbidity and mortality. Early identification of highly affected subjects within this population is of utmost importance to enable informed treatment decisions. The measurement of intima media thickness (IMT) is a readily available, non-invasive method to investigate evidence of early atherosclerosis. To assess the usefulness of this method in pediatric subjects with hypercholesterolemia, we here examined a possible interaction of LDL-C and Lp(a) on IMT.</p></div><div><h3>Methods</h3><p>Blood lipids (Lp(a), LDL-cholesterol, total cholesterol, triglycerides, high density lipoprotein (HDL) -cholesterol, apolipoprotein A1, apolipoprotein B), anthropometric parameters (age, height, weight, body mass index (BMI)) and possibly existing early evidence of atherosclerotic lesions measured by intima media thickness (IMT zscore).as a surrogate parameter was examined retrospectively in 113 children and adolescents (aged 1–18 years) with elevated Lp(a) and/or LDL-cholesterol (Lp(a) &gt; 30 mg/dL, LDL&gt;130 mg/dL). Furthermore, we compared hsCRP levels between groups.</p></div><div><h3>Results</h3><p>There were no significant differences in IMT Zscore or hsCRP between groups. Regression analysis did not reveal a statistically significant interaction between Lp(a) and LDL-C.</p></div><div><h3>Conclusions</h3><p>At the age of 6–18 years, we found no significant differences in early markers of atherosclerosis between subjects with high Lp(a)- and/or high LDL-cholesterol with no detectable synergistic effects between the two lipoproteins.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"51 ","pages":"Pages 1-7"},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/54/main.PMC10037085.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendritic cell marker Clec4a4 deficiency limits atherosclerosis progression","authors":"Rossella Bellini ,&nbsp;Annalisa Moregola ,&nbsp;Jasmine Nour ,&nbsp;Yoann Rombouts ,&nbsp;Olivier Neyrolles ,&nbsp;Patrizia Uboldi ,&nbsp;Fabrizia Bonacina ,&nbsp;Giuseppe Danilo Norata","doi":"10.1016/j.athplu.2022.12.001","DOIUrl":"10.1016/j.athplu.2022.12.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Atherogenesis results from altered lipid metabolism and impaired immune response. Emerging evidence has suggested that dendritic cells (DCs) participate to atherosclerosis-related immune response, but their impact is scarcely characterized. Clec4a4 or DCIR2 (Dendritic cell immunoreceptor 2) is a C-type lectin receptor, mainly expressed by CD8α⁻ DCs, able to modulate T cell immunity. However, whether this DC subset could play a role in the atherogenesis is still poorly understood. Thus, the aim of this study is to investigate whether the absence of Clec4a4 could affect atherosclerosis-related immune response and atherosclerosis itself.</p></div><div><h3>Methods</h3><p><em>Dcir2</em>^{<em>−/−</em>} <em>Ldlr</em>^{<em>−/−</em>} and <em>Ldlr</em>^{<em>−/−</em>} mice were fed a standard diet or cholesterol-enriched diet for 12 weeks. Subsequently, the profile of circulating and lymph nodes-resident immune cells was investigated together with the analysis of plasma lipid levels and atherosclerotic plaque extension in the aorta.</p></div><div><h3>Results</h3><p>Here, we show that <em>Clec4a4</em> expression is downregulated under hypercholesterolemia and its deficiency in <em>Ldlr</em>^−/− mice results in the reduction of atherosclerotic plaque formation, together with altered lipid metabolism and impaired myeloid immune cell distribution.</p></div><div><h3>Conclusions</h3><p>Our findings suggest a pro-atherosclerotic role of Clec4a4 in experimental atherosclerosis.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"51 ","pages":"Pages 8-12"},"PeriodicalIF":1.6,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/07/bf/main.PMC10037088.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9561069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial","authors":"Haitham Khraishah ,&nbsp;Lina Karout ,&nbsp;Sun Young Jeong ,&nbsp;Barrak Alahmad ,&nbsp;Abdelrahman AlAshqar ,&nbsp;Matthew J. Belanger ,&nbsp;Francine K. Welty ,&nbsp;Erin D. Michos ,&nbsp;Mazen Albaghdadi","doi":"10.1016/j.athplu.2022.08.003","DOIUrl":"10.1016/j.athplu.2022.08.003","url":null,"abstract":"<div><h3>Background</h3><p>Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young.</p></div><div><h3>Methods</h3><p>Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE).</p></div><div><h3>Results</h3><p>Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;<em>P</em> &lt; 0.001) and undergo coronary angiography (66.3%vs.57.3%;<em>P</em> &lt; 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;<em>P</em> &lt; 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40–0.61;<em>P</em> &lt; 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46–0.64;<em>P</em> &lt; 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0–2.45;<em>P</em> = 0.048) were higher for young women compared to men.</p></div><div><h3>Conclusion</h3><p>Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"50 ","pages":"Pages 25-31"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/eb/c4/main.PMC9833239.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TACE/ADAM17 substrates associate with ACS (Ep-CAM, HB-EGF) and follow-up MACE (TNFR1 and TNFR2)","authors":"Melody Chemaly ,&nbsp;Roisin McAllister ,&nbsp;Aaron Peace ,&nbsp;Anthony John Bjourson ,&nbsp;Steve Watterson ,&nbsp;Andrew Parton ,&nbsp;Matthias Clauss ,&nbsp;Victoria McGilligan","doi":"10.1016/j.athplu.2022.09.001","DOIUrl":"10.1016/j.athplu.2022.09.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>TACE/ADAM17 is a membrane bound metalloprotease, which cleaves substrates involved in immune and inflammatory responses and plays a role in coronary artery disease (CAD). We measured TACE and its substrates in CAD patients to identify potential biomarkers within this molecular pathway with potential for acute coronary syndrome (ACS) and major adverse cardiovascular events (MACE) prediction.</p></div><div><h3>Methods</h3><p>Blood samples were obtained from consecutive patients (n = 229) with coronary angiographic evidence of CAD admitted with ACS or electively. MACE were recorded after a median 3-year follow-up. Controls (n = 115) had a &lt;10% CAD risk as per the HeartSCORE. TACE and TIMP3 protein and mRNA levels were measured by ELISA and RT-qPCR respectively. TACE substrates were measured using a multiplex proximity extension assay.</p></div><div><h3>Results</h3><p><em>TACE</em> mRNA and cell protein levels (<em>p &lt; 0.01</em>) and TACE substrates LDLR (<em>p = 0.006</em>), TRANCE (<em>p = 0.045</em>), LAG-3 (<em>p &lt; 0.001</em>) and ACE2 (<em>p &lt; 0.001</em>) plasma levels were significantly higher in CAD patients versus controls. TACE inhibitor TIMP3 mRNA levels were significantly lower in CAD patients and tended to be lower in the ACS population (<em>p &lt; 0.05</em>). TACE substrates TNFR1 (OR:3.237,CI:1.514–6.923,<em>p = 0.002</em>), HB-EGF (OR:0.484,CI:0.288–0.813,<em>p = 0.006</em>) and Ep-CAM (OR:0.555,CI:0.327–0.829,<em>p = 0.004</em>) accurately classified ACS patients with HB-EGF and Ep-CAM levels being lower compared to electively admitted patients. TNFR1 (OR:2.317,CI:1.377–3.898,<em>p = 0.002</em>) and TNFR2 (OR:1.902,CI:1.072–3.373,<em>p = 0.028</em>) were significantly higher on admission in those patients who developed MACE within 3 years.</p></div><div><h3>Conclusions</h3><p>We demonstrate a possible role of TACE substrates LAG-3, HB-EGF and Ep-CAM in atherosclerotic plaque development and stability. We also underline the importance of measuring TNFR1 and TNFR2 earlier than previously appreciated for MACE prediction. We report an important role of TIMP3 in regulating TACE levels.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"50 ","pages":"Pages 40-49"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7c/7e/main.PMC9833260.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Periostin contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts","authors":"Zhonghua Wang ,&nbsp;Guoliang Li ,&nbsp;Mingpeng Li ,&nbsp;Lu Hu ,&nbsp;Zichen Hao ,&nbsp;Qian Li ,&nbsp;Chaofeng Sun","doi":"10.1016/j.athplu.2022.10.001","DOIUrl":"10.1016/j.athplu.2022.10.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Adventitial remodeling is an important pathological process of atherosclerosis, but cues implicated in adventitial remodeling are far from fully understood. Periostin (POSTN), a matricellular protein, has been demonstrated to have multiple roles in cardiovascular diseases. The aim of the study was to explore the function of POSTN in adventitial remodeling during atherosclerosis.</p></div><div><h3>Methods</h3><p>An atherosclerosis model was constructed based on ApoE-/- mice fed a high-fat and high-cholesterol diet. The expression of POSTN in the adventitia of mouse atherosclerotic vascular specimens was detected by immunohistochemical staining. The roles of POSTN in regulating adventitial fibroblast activation were assessed by cell contractility and activation marker α-smooth muscle actin (α-SMA) expression evaluation in adventitial fibroblasts overexpressing POSTN. In addition, we performed quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting to examine the expression of the proinflammatory chemokines transforming growth factor-β1 (TGF-β1) and monocyte chemotactic protein 1 (MCP1), as well as some extracellular matrix (ECM)-related proteins, in POSTN-overexpressing adventitial fibroblasts. Finally, the integrin-related signaling pathway was detected upon POSTN overexpression in adventitial fibroblasts.</p></div><div><h3>Results</h3><p>POSTN was highly expressed in the adventitia of atherosclerotic aortae in the mouse atherosclerosis model and promoted the activation and contraction of adventitial fibroblasts. Meanwhile, POSTN also induced adventitial fibroblasts to express TGF-β1, monocyte chemotactic protein-1 (MCP1), and ECM-related proteins and activated the phosphorylation of focal adhesion kinase (FAK) and Src.</p></div><div><h3>Conclusions</h3><p>Our results revealed that POSTN is elevated in adventitia during atherosclerosis and contributes to the adventitial remodeling of atherosclerosis by activating adventitial fibroblasts.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"50 ","pages":"Pages 57-64"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9833252/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10527345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smoking and diabetes attenuate beneficial effects of PSCK9 inhibitors on arterial wall properties in patients with very high lipoprotein (a) levels","authors":"Andreja Rehberger Likozar ,&nbsp;Miran Šebeštjen","doi":"10.1016/j.athplu.2022.07.001","DOIUrl":"10.1016/j.athplu.2022.07.001","url":null,"abstract":"<div><h3>Background and aims</h3><p>Elevated lipoprotein (a) (Lp(a)) and low-density lipoprotein cholesterol levels (LDL-C) are significant residual risk factors for cardiovascular events. Treatment with protein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduces the levels of both. Less is known about effects of PCSK9 inhibitors on functional and morphological properties of the arterial wall. The aim of the present study was to determine whether other factors besides decreased LDL-C and Lp(a) are associated with functional (flow-mediated dilation [FMD]) and morphological (carotid intima-media thickness [c-IMT], pulse-wave velocity [PWV]) changes of the arterial wall properties in patients with coronary artery disease (CAD) treated with alirocumab and evolocumab.</p></div><div><h3>Methods</h3><p>One hundred patients with CAD after myocardial infarction before 55 years and with high Lp(a) were randomised to lipid-lowering therapies without PCSK9 inhibitors (control; N = 31), or with alirocumab 150 mg SC (N = 35) or evolocumab 140 mg SC (N = 34), every 2 weeks. All patients underwent blood sampling for biochemical analyses and ultrasound measurements for FMD, c-IMT and PWV.</p></div><div><h3>Results</h3><p>There were no significant changes in FMD for the control (10.7% ± 6.6%–11.1% ± 4.4%, p = 0.716) and alirocumab (10.7% ± 5.9%–11.2% ± 5.3%, p = 0.547) groups, while evolocumab promoted significant increase (11.2% ± 6.8%–14.1% ± 6.6%, p &lt; 0.0001). Only in non-smokers and non-diabetics significant improvements in FMD (p &lt; 0.0001) after treatment with PCSK9 inhibitors were observed.</p></div><div><h3>Conclusion</h3><p>These data show that for patients with CAD and high Lp(a) levels, beneficial effects of PCSK9 inhibitors on the arterial wall properties can be attenuated by specific risk factors, such as smoking and diabetes.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":"50 ","pages":"Pages 1-9"},"PeriodicalIF":1.6,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/e0/main.PMC9833244.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10540456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}