sICAM-1 concentrations are associated with inflammation in contralateral carotid plaque in patients with ischemic stroke.

BACKGROUND: Atherosclerotic plaques in the internal carotid artery are responsible for more than 15% of ischemic strokes. Carotid 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) detects plaque inflammation. Plasma ICAM-1 and LRP1 concentrations have been associated with inflammation in ipsilateral carotid plaque. The aim of the present study was to test the association between the soluble (s) form of these biomarkers and contralateral carotid plaques. METHODS: Prospective study conducted in 53 patients with a recent ischemic stroke and at least one atherosclerotic plaque in both carotid arteries. All of the patients underwent an early carotid 18F-FDG PET, and a blood sample was obtained at 7±1 days. Several plasma inflammatory markers were evaluated by Multiplex and sLRP1 levels were measured by commercial ELISA. Bivariate and multivariable linear regression was used to assess the association between inflammatory markers and the clinical variables, including contralateral maximum standardized uptake value (SUVmax) and mean SUVmax (mean of contralateral and ipsilateral SUVmax) of 18F-FDG uptake. Hazard ratio (HR) was estimated with Cox models adjusted for potential confounding factors to evaluate recurrence. RESULTS: Multivariable linear regression analysis showed an independent association between sICAM-1 and sVCAM-1 and mean SUVmax (CI=-0.064-0.325, p=0.004; CI=0.079-0.554, p=0.010). In addition, in bivariate regression analysis, sICAM-1 was associated with contralateral SUVmax (CI=0.049-0.382, p=0.012). Cox regression showed that mean SUVmax was associated with stroke recurrence (HR=5.604, p=0.044). CONCLUSIONS: sICAM-1 was independently associated with mean carotid plaque inflammation and with inflammation in contralateral plaque. sICAM-1 could be an indicator of plaque inflammation even in asymptomatic plaques.

Apolipoprotein J protects cardiomyocytes from lipid-mediated inflammation and cytotoxicity induced by the epicardial adipose tissue of diabetic patients.

Diabetic patients present increased volume and functional alterations in epicardial adipose tissue (EAT). We aimed to analyze EAT from type 2 diabetic patients and the inflammatory and cytotoxic effects induced on cardiomyocytes. Furthermore, we analyzed the cardioprotective role of apolipoprotein J (apoJ). EAT explants were obtained from nondiabetic patients (ND), diabetic patients without coronary disease (DM), and DM patients with coronary disease (DM-C) after heart surgery. Morphological characteristics and gene expression were evaluated. Explants were cultured for 24 h and the content of nonesterified fatty acids (NEFA) and sphingolipid species in secretomes was evaluated by lipidomic analysis. Afterwards, secretomes were added to AC16 human cardiomyocytes for 24 h in the presence or absence of cardioprotective molecules (apoJ and HDL). Cytokine release and apoptosis/necrosis were assessed by ELISA and flow cytometry. The EAT from the diabetic samples showed altered expression of genes related to lipid accumulation, insulin resistance, and inflammation. The secretomes from the DM samples presented an increased ratio of pro/antiatherogenic ceramide (Cer) species, while those from DM-C contained the highest concentration of saturated NEFA. DM and DM-C secretomes promoted inflammation and cytotoxicity on AC16 cardiomyocytes. Exogenous Cer16:0, Cer24:1, and palmitic acid reproduced deleterious effects in AC16 cells. These effects were attenuated by exogenous apoJ. Diabetic secretomes promoted inflammation and cytotoxicity in cardiomyocytes. This effect was exacerbated in the secretomes of the DM-C samples. The increased content of specific NEFA and ceramide species seems to play a key role in inducing such deleterious effects, which are attenuated by apoJ.

Artificial Intelligence Assistance for the Measurement of Full Alignment Parameters in Whole-Spine Lateral Radiographs.

BACKGROUND: Measuring spinal alignment with radiological parameters is essential in patients with spinal conditions likely to be treated surgically. These evaluations are not usually included in the radiological report. As a result, spinal surgeons commonly perform the measurement, which is time-consuming and subject to errors. We aim to develop a fully automated artificial intelligence (AI) tool to assist in measuring alignment parameters in whole-spine lateral radiograph (WSL X-rays). METHODS: We developed a tool called Vertebrai that automatically calculates the global spinal parameters (GSPs): Pelvic incidence, sacral slope, pelvic tilt, L1-L4 angle, L4-S1 lumbo-pelvic angle, T1 pelvic angle, sagittal vertical axis, cervical lordosis, C1-C2 lordosis, lumbar lordosis, mid-thoracic kyphosis, proximal thoracic kyphosis, global thoracic kyphosis, T1 slope, C2-C7 plummet, spino-sacral angle, C7 tilt, global tilt, spinopelvic tilt, and hip odontoid axis. We assessed human-AI interaction instead of AI performance alone. We compared the time to measure GSP and inter-rater agreement with and without AI assistance. Two institutional datasets were created with 2267 multilabel images for classification and 784 WSL X-rays with reference standard landmark labeled by spinal surgeons. RESULTS: Vertebrai significantly reduced the measurement time comparing spine surgeons with AI assistance and the AI algorithm alone, without human intervention (3 minutes vs. 0.26 minutes; P < 0.05). Vertebrai achieved an average accuracy of 83% in detecting abnormal alignment values, with the sacral slope parameter exhibiting the lowest accuracy at 61.5% and spinopelvic tilt demonstrating the highest accuracy at 100%. Intraclass correlation analysis revealed a high level of correlation and consistency in the global alignment parameters. CONCLUSIONS: Vertebrai's measurements can accurately detect alignment parameters, making it a promising tool for measuring GSP automatically.

PCSK9 plasma concentration is associated with epicardial adipose tissue volume and metabolic control in patients with type 1 diabetes.

Patients with type 1 diabetes (T1D) have a greater risk of cardiovascular disease. Proconvertase subtilisin-kexin 9 (PCSK9) is involved in the atherosclerosis process. This study aimed to determine the relationship between PCSK9 levels and epicardial adipose tissue (EAT) volume and cardiometabolic variables in patients with T1D. This was an observational cross-sectional study including 73 patients with T1D. Clinical, biochemical and imaging data were collected. We divided the patients into two groups according to their glycemic control and the EAT index (iEAT) percentile. We performed a correlation analysis between the collected variables and PCSK9 levels; subsequently, we performed a multiple regression analysis with the significant parameters. The mean age was 47.6 ± 8.5 years, 58.9% were men, and the BMI was 26.9 ± 4.6 kg/m2. A total of 31.5%, 49.3% and 34.2% of patients had hypertension, dyslipidemia and smoking habit, respectively. The PCSK9 concentration was 0.37 ± 0.12 mg/L, which was greater in patients with worse glycemic control (HbA1c > 7.5%), dyslipidemia and high EAT volume (iEAT > 75th percentile). The PCSK9 concentration was positively correlated with age (r = 0.259; p = 0.027), HbA1c (r = 0.300; p = 0.011), insulin dose (r = 0.275; p = 0.020), VLDL-C level (r = 0.331; p = 0.004), TG level (r = 0.328; p = 0.005), and iEAT (r = 0.438; p < 0.001). Multiple regression analysis revealed that 25% of the PCSK9 variability was explained by iEAT and HbA1c (p < 0.05). The PCSK9 concentration is associated with metabolic syndrome parameters, poor glycemic control and increased EAT volume in patients with T1D.

Inteligencia artificial. Aplicación en las imágenes cardiovasculares y la prevención cardiovascular / Artificial Intelligence in Cardiovascular Imaging and Cardiovascular Prevention

RESUMEN La inteligencia artificial (IA) está basada en programas computacionales que pueden imitar el pensamiento humano y automatizar algunos procesos. En el ámbito médico se está estudiando hace más de 50 años, pero en los últimos años el crecimiento ha sido exponencial. El campo de las imágenes cardiovasculares es particularmente atractivo para aplicarla, dado que, guiadas por IA, personas no expertas pueden adquirir imágenes completas, automatizar procesos y mediciones, orientar diagnósticos, detectar hallazgos no visibles al ojo humano, realizar diagnósticos oportunistas de afecciones no buscadas en el estudio índice pero evaluables a través de las imágenes disponibles, o identificar patrones de asociación dentro de una gran cantidad de datos como fuente de generación de hipótesis. En el campo de la prevención cardiovascular, la IA se ha aplicado en diferentes escenarios con fines diagnósticos, pronósticos y terapéuticos en el manejo de algunos factores de riesgo cardiovascular, como las dislipidemias o la hipertensión arterial. Si bien existen limitaciones con el uso de la IA tales como el costo, la accesibilidad y la compatibilidad de los programas, la validez externa de los resultados en determinadas poblaciones, o algunos aspectos éticos-legales (privacidad de los datos), esta tecnología está en crecimiento vertiginoso y posiblemente revolucione la práctica médica actual.

ABSTRACT Artificial intelligence (AI) is based on computer programs that imitate human thinking and automate certain processes. Artificial intelligence has been studied in the medical field for over 50 years, but in recent years, its growth has been exponential. The field of cardiovascular imaging is particularly attractive since AI can guide non-experts in image acquisition, automate processes and measurements, guide diagnoses, detect findings not visible to the human eye, make opportunistic diagnoses of unexpected conditions in the index test, or identify patterns of association within a large amount of data as a source of hypothesis generation. In the field of cardiovascular prevention, AI has been used for diagnostic, prognostic, and therapeutic purposes in managing cardiovascular risk factors such as dyslipidemia and hypertension. While there are limitations to the use of AI, such as cost, accessibility, compatibility of programs, external validity of results in certain populations, and ethical-legal aspects such as data privacy, this technology is rapidly growing and is likely to revolutionize current medical practice.

Automatic Speech Recognition System to Record Progress Notes in a Mobile EHR: A Pilot Study.

Creating notes in the EHR is one of the most problematic aspects for health professionals. The main challenges are the time spent on this task and the quality of the records. Automatic speech recognition technologies aim to facilitate clinical documentation for users, optimizing their workflow. In our hospital, we internally developed an automatic speech recognition system (ASR) to record progress notes in a mobile EHR. The objective of this article is to describe the pilot study carried out to evaluate the implementation of ASR to record progress notes in a mobile EHR application. As a result, the specialty that used ASR the most was Home Medicine. The lack of access to a computer at the time of care and the need to perform short and fast evolutions were the main reasons for users to use the system.

Integrating Dermoscopic Images into PACS Using DICOM and Modality Worklist.

Dermatology is one of the medical fields outside the radiology service that uses image acquisition and analysis in its daily medical practice, mostly through digital dermoscopy imaging modality. The acquisition, transfer, and storage of dermatology images has become an important issue to resolve. We aimed to describe our experience in integrating dermoscopic images into PACS using DICOM as a guide for the health informatics and dermatology community. During 2022 we integrated the video dermoscopy equipment through a strategic plan with an 8-step procedure. We used the DICOM standard with Modality Worklist and Storage commitment. Three systems were involved (video dermoscopy software, the EHR, and PACS). We identified critical steps and faced many challenges, such as the lack of a final model of DICOM standard for dermatology images.

Development of an ASR System for Medical Conversations.

In this work we document the development of an ASR system for the transcription of conversations between patient and doctor and we will point out the critical aspects of the domain. The system was trained with an acoustic base of spontaneous speech that has a domain language model and a supervised phonetic dictionary. Its performance was compared with two systems: a) NeMo End-to-End Conformers in Spanish and b) Google API ASR (Automatic Speech Recognition) Cloud. The evaluation was carried out on a set of 208 teleconsultations recorded during the year 2020. The WER (Word Error Rate) was evaluated in ASR, and Recall and F1 for recognized medical entities. In conclusion, the developed system performed better, reaching 72.5% accuracy in the domain of teleconsultations and an F1 for entity recognition of 0.80.

Bioinformatics Architecture for Integrating Genomics Data into Electronic Health Records.

The adequate management of patients' genomic information is essential for any health institution pursuing the Precision Medicine model. Here we approach a bioinformatic architecture that allows the Institution to store its whole genetic test data in a scalable database, and also the integration of that genetic data with the Electronic Health Record through a Clinical Decision Support System. The system complements patient care by suggesting referral to genetic counseling for patients who are potentially at risk of hereditary breast/ovarian cancer, and allowing for proper follow-up of patients with pathogenic variants in BRCA1 or BRCA2 genes. The implemented solution uses the FHIR standard and genetic nomenclatures from the Human Genome Variation Society and the HUGO Gene Nomenclature Committee. The architecture is flexible enough to allow any other health institution to integrate -to their information ecosystem- the whole solution or some of the modules according to its degree of digitization progress.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

A dataset of skin lesion images collected in Argentina for the evaluation of AI tools in this population.

In recent years, numerous dermatological image databases have been published to make possible the development and validation of artificial intelligence-based technologies to support healthcare professionals in the diagnosis of skin diseases. However, the generation of these datasets confined to certain countries as well as the lack of demographic information accompanying the images, prevents having a real knowledge of in which populations these models could be used. Consequently, this hinders the translation of the models to the clinical setting. This has led the scientific community to encourage the detailed and transparent reporting of the databases used for artificial intelligence developments, as well as to promote the formation of genuinely international databases that can be representative of the world population. Through this work, we seek to provide details of the processing stages of the first public database of dermoscopy and clinical images created in a hospital in Argentina. The dataset comprises 1,616 images corresponding to 1,246 unique lesions collected from 623 patients.

Novel Therapeutic Approaches to Prevent Atherothrombotic Ischemic Stroke in Patients with Carotid Atherosclerosis.

Atherothrombotic stroke represents approximately 20% of all ischemic strokes. It is caused by large-artery atherosclerosis, mostly in the internal carotid artery, and it is associated with a high risk of early recurrence. After an ischemic stroke, tissue plasminogen activator is used in clinical practice, although it is not possible in all patients. In severe clinical situations, such as high carotid stenosis (≥70%), revascularization by carotid endarterectomy or by stent placement is carried out to avoid recurrences. In stroke prevention, the pharmacological recommendations are based on antithrombotic, lipid-lowering, and antihypertensive therapy. Inflammation is a promising target in stroke prevention, particularly in ischemic strokes associated with atherosclerosis. However, the use of anti-inflammatory strategies has been scarcely studied. No clinical trials are clearly successful and most preclinical studies are focused on protection after a stroke. The present review describes novel therapies addressed to counteract inflammation in the prevention of the first-ever or recurrent stroke. The putative clinical use of broad-spectrum and specific anti-inflammatory drugs, such as monoclonal antibodies and microRNAs (miRNAs) as regulators of atherosclerosis, will be outlined. Further studies are necessary to ascertain which patients may benefit from anti-inflammatory agents and how.

Radiomics and Machine Learning for prediction of two-year disease-specific mortality and KRAS mutation status in metastatic colorectal cancer.

PURPOSE: Colorectal cancer is usually accompanied by liver metastases. The prediction of patient evolution is essential for the choice of the appropriate therapy. The aim of this study is to develop and evaluate machine learning models to predict KRAS gene mutations and 2-year disease-specific mortality from medical images. METHODS: Clinical and follow-up information was collected from patients with metastatic colorectal cancer who had undergone computed tomography prior to liver resection. The dominant liver lesion was segmented in each scan and radiomic features were extracted from the volumes of interest. The 65% of the cases were employed to perform feature selection and to train machine learning algorithms through cross-validation. The best performing models were assembled and evaluated in the remaining cases of the cohort. RESULTS: For the mortality model development, 101 cases were used as training set (64 alive, 37 deceased) and 35 as test set (22 alive, 13 deceased); while for KRAS mutation models, 55 cases were used for training (31 wild-type, 24 mutated) and 30 for testing (17 wild-type, 13 mutated). The ensemble of top performing models resulted in an area under the receiver operating characteristic curve of 0.878 for mortality and 0.905 for KRAS prediction. CONCLUSIONS: Predicting the prognosis of patients with metastatic colorectal cancer is useful for making timely decisions about the best treatment options. This study presents a noninvasive method based on quantitative analysis of baseline images to identify factors influencing patient outcomes, with the aim of incorporating these tools as support systems.

Increased sLRP1 and decreased atrial natriuretic peptide plasma levels in newly diagnosed T2DM patients are normalized after optimization of glycemic control.

Background: Low-density lipoprotein receptor-related protein 1 (LRP1) negatively modulates circulating atrial natriuretic peptide (ANP) levels. Both molecules are involved in the regulation of cardiometabolism. Objectives: To evaluate soluble LRP1 (sLRP1) and ANP levels in people with newly diagnosed type 2 diabetes mellitus (T2DM) and determine the effects of metabolic optimization. Methods: This single-center longitudinal observational study recruited patients with newly diagnosed T2DM (n = 29, HbA1c > 8.5%), and 12 healthy control, age- and sex-matched volunteers. sLRP1 and ANP levels were measured by immunoassays at T2DM onset and at one year after optimization of glycemic control (HbA1c ≤ 6.5%). Results: T2DM had higher sLRP1 levels than the control group (p = 0.014) and lower ANP levels (p =0.002). At 12 months, 23 T2DM patients reached the target of HbA1c ≤ 6.5%. These patients significantly reduced sLRP1 and increased ANP levels. Patients who did not achieve HbA1c < 6.5% failed to normalize sLRP1 and ANP levels. There was an inverse correlation in the changes in sLRP1 and ANP (p = 0.031). The extent of sLRP1 changes over 12 months of metabolic control positively correlated with those of total cholesterol, LDL cholesterol, TG, TG/HDLc, and apolipoprotein B. Conclusions: Newly diagnosed T2DM patients have an increased sLRP1/ANP ratio, and increased sLRP1 and decreased ANP levels are normalized in the T2DM patients that reached an strict glycemic and metabolic control. sLRP1/ANP ratio could be a reliable marker of cardiometabolic function.

Special Issue: New Insight into the Molecular Role of Lipids and Lipoproteins in Vascular Diseases.

Lipids and lipoproteins play a key role in cardiovascular diseases (CVD), mainly in the development of atherosclerosis [...].

El diagnóstico precoz de las enfermedades reumáticas, necesidades reales

Introducción: Las enfermedades reumáticas son conceptualizadas como un grupo de afecciones que generan grados variables de discapacidad funcional y disminución de la percepción de calidad de vida relacionada con la salud. Su diagnóstico precoz resulta vital para minimizar el riesgo de aparición de complicaciones y deformidades articulares. Objetivo: Identificar el nivel de conocimiento sobre los elementos básicos del diagnóstico de enfermedades reumáticas en médicos del primer nivel de atención de salud. Métodos: Se realizó una investigación básica, no experimental, descriptiva y transversal. El universo estuvo constituido por 428 médicos generales que laboran en el primer nivel de atención de salud de la zona 3 en Ecuador. La muestra quedó conformada por 204 profesionales. Se aplicó un modelo de recolección de información que permitió identificar características generales y nivel de conocimiento sobre elementos básicos del diagnóstico de las enfermedades reumáticas. Resultados: Promedio de edad de 28,39 años, predominio de médicos femeninas (63,24 %), entre 4 y 6 años de graduados (35,78 %) y haber recibido capacitaciones sobre los elementos básicos del diagnóstico de las enfermedades reumáticas (98,04 %). El nivel de conocimiento predominante sobre este tema fue el bajo (89,70 %). Conclusiones: El nivel de conocimiento sobre elementos básicos del diagnóstico de enfermedades reumáticas en médicos del primer nivel de atención de salud es bajo.

Introduction: Rheumatic diseases are conceptualized as a group of conditions that generate variable degrees of functional disability and decreased perception of health-related quality of life. Its early diagnosis is vital to minimize the risk of complications and joint deformities. Objective: To identify the level of knowledge about the basic elements of the diagnosis of rheumatic diseases in doctors of the first level of health care. Methods: A basic, non-experimental, descriptive and cross-sectional investigation was carried out. The universe consisted of 428 general practitioners who work in the first level of health care in zone 3 in Ecuador. The sample was made up of 204 professionals. An information collection model was applied that allowed the identification of general characteristics and level of knowledge about basic elements of the diagnosis of rheumatic diseases. Results: Average age of 28.39 years, predominance of female doctors (63.24 %), between 4 and 6 years of graduation (35.78 %) and having received training on the basic elements of diagnosis of rheumatic diseases (98.04 %). The predominant level of knowledge on this topic was low (89.70 %). Conclusions: The level of knowledge about basic elements of the diagnosis of rheumatic diseases in doctors of the first level of health care is low.

Can Electronegative LDL Act as a Multienzymatic Complex?

Electronegative LDL (LDL(-)) is a minor form of LDL present in blood for which proportions are increased in pathologies with increased cardiovascular risk. In vitro studies have shown that LDL(-) presents pro-atherogenic properties, including a high susceptibility to aggregation, the ability to induce inflammation and apoptosis, and increased binding to arterial proteoglycans; however, it also shows some anti-atherogenic properties, which suggest a role in controlling the atherosclerotic process. One of the distinctive features of LDL(-) is that it has enzymatic activities with the ability to degrade different lipids. For example, LDL(-) transports platelet-activating factor acetylhydrolase (PAF-AH), which degrades oxidized phospholipids. In addition, two other enzymatic activities are exhibited by LDL(-). The first is type C phospholipase activity, which degrades both lysophosphatidylcholine (LysoPLC-like activity) and sphingomyelin (SMase-like activity). The second is ceramidase activity (CDase-like). Based on the complementarity of the products and substrates of these different activities, this review speculates on the possibility that LDL(-) may act as a sort of multienzymatic complex in which these enzymatic activities exert a concerted action. We hypothesize that LysoPLC/SMase and CDase activities could be generated by conformational changes in apoB-100 and that both activities occur in proximity to PAF-AH, making it feasible to discern a coordinated action among them.

Association of candidate genetic variants and circulating levels of ApoE/ApoJ with common neuroimaging features of cerebral amyloid angiopathy.

Introduction: Cerebral amyloid angiopathy (CAA) is characterized by the accumulation of amyloid-ß (Aß) in brain vessels and is a main cause of lobar intracerebral hemorrhage (ICH) in the elderly. CAA is associated with magnetic resonance imaging (MRI) markers of small vessel disease (SVD). Since Aß is also accumulated in Alzheimer's disease (AD) in the brain parenchyma, we aimed to study if several single nucleotide polymorphisms (SNPs) previously associated with AD were also associated with CAA pathology. Furthermore, we also studied the influence of APOE and CLU genetic variants in apolipoprotein E (ApoE) and clusterin/apolipoprotein J (ApoJ) circulating levels and their distribution among lipoproteins. Methods: The study was carried out in a multicentric cohort of 126 patients with lobar ICH and clinical suspicion of CAA. Results: We observed several SNPs associated with CAA neuroimaging MRI markers [cortical superficial siderosis (cSS), enlarged perivascular spaces in the centrum semiovale (CSO-EPVS), lobar cerebral microbleeds (CMB), white matter hyperintensities (WMH), corticosubcortical atrophy and CAA-SVD burden score]. Concretely, ABCA7 (rs3764650), CLU (rs9331896 and rs933188), EPHA1 (rs11767557), and TREML2 (rs3747742) were significantly associated with a CAA-SVD burden score. Regarding circulating levels of apolipoproteins, protective AD SNPs of CLU [rs11136000 (T) and rs9331896 (C)] were significantly associated with higher HDL ApoJ content in the lobar ICH cohort. APOEε2 carriers presented higher plasma and LDL-associated ApoE levels whereas APOEε4 carriers presented lower plasma ApoE levels. Additionally, we observed that lower circulating ApoJ and ApoE levels were significantly associated with CAA-related MRI markers. More specifically, lower LDL-associated ApoJ and plasma and HDL-associated ApoE levels were significantly associated with CSO-EPVS, lower ApoJ content in HDL with brain atrophy and lower ApoE content in LDL with the extent of cSS. Discussion: This study reinforces the relevance of lipid metabolism in CAA and cerebrovascular functionality. We propose that ApoJ and ApoE distribution among lipoproteins may be associated with pathological features related to CAA with higher ApoE and ApoJ levels in HDL possibly enhancing atheroprotective, antioxidative, and anti-inflammatory responses in cerebral ß-amyloidosis.

Circulating lipoprotein-carried miRNome analysis reveals novel VLDL-enriched microRNAs that strongly correlate with the HDL-microRNA profile.

Lipoproteins have been described as microRNAs (miRNAs) carriers. Unfortunately, the bibliography on this topic is scarce and shows a high variability between independent investigations. In addition, the miRNA profiles of the LDL and VLDL fractions have not been completely elucidated. Here, we profiled the human circulating lipoprotein-carried miRNome. Lipoprotein fractions (VLDL, LDL and HDL) were isolated from the serum of healthy subjects by ultracentrifugation and purified by size-exclusion chromatography. A panel of 179 miRNAs commonly expressed in circulation was evaluated in the lipoprotein fractions using quantitative real-time PCR (qPCR) assays. A total of 14, 4 and 24 miRNAs were stably detected in the VLDL, LDL and HDL fractions, respectively. VLDL- and HDL-miRNA signatures were highly correlated (rho 0.814), and miR-16-5p, miR-142-3p, miR-223-3p and miR-451a were among the top 5 expressed miRNAs in both fractions. miR-125a-5p, miR-335-3p and miR-1260a, were detected in all lipoprotein fractions. miR-107 and miR-221-3p were uniquely detected in the VLDL fraction. HDL showed the larger number of specifically detected miRNAs (n = 13). Enrichment in specific miRNA families and genomic clusters was observed for HDL-miRNAs. Two sequence motifs were also detected for this group of miRNAs. Functional enrichment analysis including the miRNA signatures from each lipoprotein fraction suggested a potential role in mechanistic pathways previously associated with cardiovascular disease: fibrosis, senescence, inflammation, immune response, angiogenesis, and cardiomyopathy. Collectively, our results not only support the role of lipoproteins as circulating miRNA carriers but also describe for the first time the role of VLDL as a miRNA transporter.

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis.

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.