Influencia del estrés oxidativo en la evolución de la aterosclerosis carotídea / Influence of oxidative stress on the progression of carotid atherosclerosis

Introducción y objetivo: el estrés oxidativo (EO) ha demostrado clara influencia en el desarrollo de las placas de ateroma por daños provocados en endotelio vascular. El objetivo de este trabajo es realizar un estudio de los principales marcadores de estrés oxidativo en pacientes con enfermedad aterosclerótica de la arteria carótida como signo de vulnerabilidad, analizar la implicación de la situación redox y el estado metabólico mitocondrial en patología aterosclerótica de la arteria carótida y su relación con clínica neurológica. Pacientes y métodos: se estudiaron las placas de ateroma obtenidas de pacientes intervenidos de endarectomía carotídea (asintomáticos y sintomáticos) en el Servicio de Angiología del Hospital Clínico Universitario de Valladolid en el año 2020. Se recogieron variables clínicas y demográficas y la existencia de sintomatología neurológica. Las características anatómicas y hemodinámicas se estudiaron mediante estudio eco Doppler y angiografía mediante tomografía computarizada en el preoperatorio. Se analizaron placas de ateroma como estimadores del grado de peroxidación lipídica que reflejaron el estado redox. Se ha estimado un tamaño muestral de 45 muestras en cada grupo, con una tasa de pérdidas de seguimiento del 5 %. Se estudiaron las diferencias entre los grupos mediante χ2 y la t de Student para determinar relación entre el potencial redox con las características morfológicas de placa de ateroma. Se utilizó el programa estadístico SPSS 27.0, aceptando como significativo un valor p < 0,05. Resultados: las placas de ateroma calcificadas mostraron mayor capacidad antioxidante con respecto a las placas de ateroma no calcificadas en el parámetro ABTS: 2,2-ácino-bis(ácido 3-etilbenzotiazolina-6-sulfónico) (2635,08 frente a 2803,28). La relación es estadísticamente significativa (p = 0,007)...(AU)

Introduction and objective: oxidative Stress (OS) has proven to have a clear impact on the development of atherosclerotic plaques due to the damage it causes to vascular endothelium. The aim of this study is to conduct a research on key oxidative stress markers in patients with carotid artery atherosclerotic disease as a sign of vulnerability, analyze the implications of the redox status and mitochondrial metabolic state in carotid artery atherosclerotic disease, and its relationship with neurological clinical presentation. Patients and methods: atherosclerotic plaques obtained from carotid endarterectomy patients (both asymptomatic and symptomatic) performed the Department of Angiology, Vascular and Endovascular Surgery of Hospital Clinico Universitario de Valladolid, Spain in 2020 will be examined. The clinical-demographic variables and the presence of neurological symptoms will be recorded. Anatomical and hemodynamic characteristics will be studied using Doppler ultrasound and coronary computed tomography angiography (CCTA) preoperatively. Atherosclerotic plaques will be analyzed as estimators of the degree of lipid peroxidation showing the redox state. A sample size of 45 speciments from each group has been estimated with a loss to follow-up rate of 5 %. Inter-group differences will be studied using the chi-square and Student’s t tests to establish the relationship between redox potential and morphological characteristics of the atheromatous plaque. SPSS 27.0 statistical software will be used, with a significance level set at p < 0.05. Results: calcified atherosclerotic plaques showed higher antioxidant capacity compared to non-calcified plaques in the ABTS parameter (2,2-azino-bis(3-ethylbenzthioziozline-6-sulfonic)) (2635.08 vs 2803.28), with statistically significant relationship (p = 0.007). They also exhibited greater antioxidant defense when analyzing catalase activity (160.73 vs 175.13) and SOD activity (1.11 vs 1.49) (p = 0.049)...(AU)

Lower Expression of Genes Involved in Protection against Oxidative Stress in Symptomatic Carotid Atherosclerosis.

BACKGROUND: Oxidative stress is increased in atherosclerosis, manifested both in blood and tissue (atherosclerotic plaque). We aim at describing the expression of a number of genes related to oxidative stress response in carotid atherosclerotic plaques and their relation to symptomatic state. METHODS: We have studied the messenger RNA expression levels for genes related to oxidative stress in a population of 44 patients undergoing carotid endarterectomy, according to the presence (24 patients) or absence (20 patients) of symptoms. Samples were homogenized, RNA was extracted, and gene expression was measured by quantitative reverse transcription polymerase chain reaction arrays. RESULTS: Data showed a decrease in expression of oxidative stress protective genes in symptomatic patients and increased expression of pro-oxidant genes. Asymptomatic patients maintain higher levels of expression of protective genes in the tissue. CONCLUSIONS: This study establishes a close relationship between symptoms and levels of expression of genes that protect against oxidative stress. We propose the existence of a mechanism that silences these genes, causing a more severe atherosclerotic disease state.

Early detection of high oxidative activity in patients with adenomatous intestinal polyps and colorectal adenocarcinoma: myeloperoxidase and oxidized low-density lipoprotein in serum as new markers of oxidative stress in colorectal cancer.

OBJECTIVES: To detect whether signs of oxidative stress appear at early stages of colorectal adenocarcinoma (CRC), particularly in the polyp stage. We also aimed to evaluate the specific entities myeloperoxidase (MPO) and oxidized low-density lipoprotein (oxLDL) as novel markers of oxidation in the plasma of patients with CRC and to study the relationship between oxidative status in plasma and patient survival. METHODS: We assayed serum or plasma specimens from healthy control subjects (n = 14), from patients with intestinal polyps (n = 39), and from patients with CRC (n = 128) to calculate the modified oxidative balance score (MOBS) using several serum markers (ß-carotene, lycopene, vitamin A, vitamin E, MPO, and oxLDL). We also assayed the levels of C-reactive protein (CRP) and obtained lipid profiles. Finally, we studied the survival of patients in relationship to oxidative status (antioxidants and pro-oxidants) and inflammation markers, and added theses data to the lipid profile for each patient. RESULTS: Oxidative stress levels increased as disease stage advanced. This increase was detected early in the polyp stage, before polyps progressed to cancer, and could be measured by the increase of such new markers as MPO and oxLDL, the decrease in antioxidants, and the MOBS value. Higher levels of oxidation correlated with lower survival. CONCLUSION: The oxidation process, which can cause mutations leading to CRC, begins development in the polyp stage. This process may be detected early by monitoring serum markers such as MPO and oxLDL.

Prognostic significance of an elevated neutrophil-lymphocyte ratio in the amputation-free survival of patients with chronic critical limb ischemia.

BACKGROUND: The aim of this study was to investigate the utility of admission neutrophil-lymphocyte ratio (NLR) in predicting the amputation-free survival (AFS) of patients with critical limb ischemia (CLI) who underwent an elective infrainguinal therapeutic intervention. METHODS: All patients with CLI undergoing elective infrainguinal vascular surgery (open or endovascular) at a single university teaching hospital between January 2005 and December 2009 were retrospectively identified from a prospectively maintained database. The primary end point was AFS. The cut-off of NLR >5 was used to categorize patients into low- and high-NLR groups. Kaplan-Meier analysis and long-rank test were used to compare survival between both groups. Cox regression analysis was conducted to determine independent factors affecting the AFS. RESULTS: During a median follow-up of 31 months, 561 patients with chronic CLI underwent infrainguinal revascularization. Five-year mortality was lower in the NLR <5 group (33%) than in the NLR >5 group (49%) (P ≤ 0.001), and the AFS was significantly higher in the NLR <5 group (50%) than in the NLR >5 group (26%) (P ≤ 0.001). In a multivariate analysis, preoperative NLR >5 was independently associated with 5-year AFS (hazard ratio 2.325, 95% CI 1.732-3.121). CONCLUSIONS: Elevated NLR predicts a worse AFS in patients undergoing infrainguinal vascular revascularization with chronic CLI, suggesting that the NLR conveys powerful prognostic information that is independent of other conventional clinical risk factors.

Expression and potential role of apolipoprotein D on the death-survival balance of human colorectal cancer cells under oxidative stress conditions.

PURPOSE: Inverse correlations of apolipoprotein D (ApoD) expression with tumor growth have been shown, therefore proposing ApoD as a good prognostic marker for diverse cancer types, including colorectal cancer (CRC). Besides, ApoD expression is boosted upon oxidative stress (OS) in many pathological situations. This study aims at understanding the role of ApoD in the progression of human CRC. METHODS: Samples of CRC and distant normal tissue (n = 51) were assayed for levels of lipid peroxidation, expression profile of OS-dependent genes, and protein expression. Three single-nucleotide polymorphisms in the ApoD gene were analyzed (n = 139), with no significant associations found. Finally, we assayed the effect of ApoD in proliferation and apoptosis in the CRC HT-29 cell line. RESULTS: In CRC, lipid peroxides increase while ApoD messenger RNA and protein decrease through tumor progression, with a prominent decrease in stage I. In normal mucosa, ApoD protein is present in lamina propia and enteroendocrine cells. In CRC, ApoD expression is heterogeneous, with low expression in stromal cells commonly associated with high expression in the dysplastic epithelium. ApoD promoter is basally methylated in HT-29 cells but retains the ability to respond to OS. Exogenous addition of ApoD to HT-29 cells does not modify proliferation or apoptosis levels in control conditions, but it promotes apoptosis upon paraquat-induced OS. CONCLUSION: Our results show ApoD as a gene responding to OS in the tumor microenvironment. Besides using ApoD as marker of initial stages of tumor progression, it can become a therapeutic tool promoting death of proliferating tumor cells suffering OS.