Plasma lipidome differences in patients with and without significant carotid plaque.

BACKGROUND: Atherosclerosis is a major cause of ischemic stroke, and early detection of advanced atherosclerosis in the carotid artery is important for reducing morbidity and mortality. What is even more important is not only detection of atherosclerosis but early determination whether the patients are at high risk of an event with adverse effects as the size of the plaque does not necessarily reflect its potential to trigger such events. AIM: We studied whether plasma lipidomics profile can be used as a diagnostic tool for stratification of stable or unstable plaques without the need of removing the carotid plaque. METHODS: This study used liquid chromatography high-resolution tandem mass spectrometry lipidomics to characterize lipid profiles in patients' plasma and found that patients with significant and complicated (vulnerable) atherosclerotic plaque had distinct lipid profiles compared to those with insignificant plaques. RESULTS: The lipid classes that were most predictive of vulnerable plaque were lysophosphoethanolamines, fatty acyl esters of hydroxy fatty acids, free fatty acids, plasmalogens, and triacylglycerols. Most of these compounds were found decreased in plasma of patients with unstable plaques which enabled sufficient performance of a statistical model used for patient stratification. CONCLUSIONS: Plasma lipidomes measured by liquid chromatography-mass spectrometry show differences in patients with stable and unstable carotid plaques, therefore these compounds could potentially be used as biomarkers for unstable plaque in future clinical diagnosis.

Exploring the Role of GDF-15 in Inflammatory Bowel Disease: A Case-Controlled Study Comparing Crohn's Disease and Ulcerative Colitis with Non-Inflammatory Controls.

Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.

Oxidative Stress as a Reliable Biomarker of Carotid Plaque Instability: A Pilot Study.

Background: Predicting stroke risk in patients with carotid artery stenosis (CS) remains challenging. Circulating biomarkers seem to provide improvements with respect to risk stratification. Methods: Study patients who underwent carotid endarterectomy were categorized into four groups according to symptomatology and compared as follows: symptomatic with asymptomatic patients; and asymptomatic patients including amaurosis fugax (AF) (asymptomatic + AF group) with patients with a transient ischemic attack (TIA) or brain stroke (BS) (hemispheric brain stroke group). Carotid specimens were histologically analyzed and classified based on the American Heart Classification (AHA) standard. As a marker of OS, the plasma levels of malondialdehyde (MDA) were measured. Comparisons of MDA plasma levels between groups were analyzed. Results: In total, 35 patients were included in the study. There were 22 (63%) patients in the asymptomatic group and 13 (37%) in the symptomatic group. Atheromatous plaque (p = 0.03) and old hemorrhage (p = 0.05), fibrous plaque (p = 0.04), myxoid changes (p = 0.02), plaques without hemorrhage (p = 0.04), significant neovascularization (p = 0.04) and AHA classification (p = 0.006) had significant correlations with clinical presentation. There were 26 (74%) patients in the asymptomatic group and 9 (26%) in the hemispheric brain stroke group. Atheromatous plaque (p = 0.02), old hemorrhage (p = 0.05) and plaques without neovascularization (p = 0.02), fibrous plaque (p = 0.03), plaques without hemorrhage (p = 0.02) and AHA classification (p = 0.01) had significant correlations with clinical presentation. There was no significant difference between symptomatic and asymptomatic groups with respect to MDA plasma levels (p = 0.232). A significant difference was observed when MDA plasma levels were compared to asymptomatic + AF and the hemispheric stroke group (p = 0.002). Conclusions: MDA plasma level correlates with the risk of hemispheric stroke (TIA or BS) and is a reliable marker of plaque vulnerability in carotid artery stenosis.

Long-Term Effects on the Lipidome of Acute Coronary Syndrome Patients.

Lipids modified by oxidative stress are key players in atherosclerosis progression. Superimposed thrombosis with subsequent closure of the coronary artery leads to the clinical manifestation of acute coronary syndrome (ACS). While several studies focusing on alterations in lipid metabolism in the acute phase have been conducted, no information is available on patients' lipidome alterations over longer time periods. In the current follow-up study, we analyzed plasma samples obtained from 17 patients three years after their ACS event (group AC). Originally, these patients were sampled 3-5 days after an index event (group B). Lipidome stability over time was studied by untargeted lipidomics using high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). Multi-dimensional statistics used for data processing indicated that plasmalogen lipids were the most prominent lipids separating the above patient groups and that they increased in the follow-up AC group. A similar trend was observed for lysophosphatidylethanolamine (LPE) and phosphatidylethanolamine (PE). The opposite trend was observed for two fatty acyls of hydroxy fatty acid (FAHFAs) lipids and free stearic acid. In addition, a decrease in the "classic" oxitadive stress marker, malondialdehyde (MDA), occurred during the follow-up period. Our findings present unique information about long-term lipidome changes in patients after ACS.

Incorporation of Fibrin, Platelets, and Red Blood Cells into a Coronary Thrombus in Time and Space.

We describe the internal structure, spatial organization and dynamic formation of coronary artery thrombi from ST-segment elevation myocardial infarction patients. Scanning electron microscopy (SEM) revealed significant differences among four groups of patients (<2 hours; 2-6 hours; 6-12 hours, and >12 hours) related to the time of ischemia. Coronary artery thrombi from patients presenting less than 2 hours after the infarction were almost entirely composed of platelets, with small amounts of fibrin and red blood cells. In contrast, thrombi from late presenters (>12 hours) consisted of mainly platelets at the distal end, where clotting was initiated, with almost no platelets at the proximal end, while the red blood cell content went from low at the initiating end to more than 90% at the proximal end. Furthermore, fibrin was present mainly on the outside of the thrombi and older thrombi contained thicker fibers. The red blood cells in late thrombi were compressed to a close-packed, tessellated array of polyhedral structures, called polyhedrocytes. Moreover, there was redistribution from the originally homogeneous composition to fibrin and platelets to the outside, with polyhedrocytes on the interior. The presence of polyhedrocytes and the redistribution of components are signs of in vivo clot contraction (or retraction). These results suggest why later thrombi are resistant to fibrinolytic agents and other treatment modalities, since the close-packed polyhedrocytes form a nearly impermeable seal. Furthermore, it is of particular clinical significance that these findings suggest specific disparate therapies that will be most effective at different stages of thrombus development.

Lipidomic Analysis to Assess Oxidative Stress in Acute Coronary Syndrome and Acute Stroke Patients.

Alterations in lipid metabolism mediated by oxidative stress play a key role in the process of atherosclerosis and superimposed thrombosis; these can lead to acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Multiple studies have shown that the formation of atheromatous lesions is initiated by oxidation of low-density lipoproteins incorporated into the intima of the vessel wall. Here, we studied lipids in plasma samples from three cohorts: 61 patients with ACS (group A), 49 patients with AIS (group D), and 82 controls (group K). Untargeted lipidomics based on high-performance liquid chromatography coupled to mass spectrometry (UHPLC-HRMS) was employed to obtain comprehensive information on whether relationships exist between these patient categories based on lipid patterns. In addition, malondialdehyde (MDA) as a standard marker of oxidative stress was monitored. The most characteristic lipids in group K were fatty acyls of hydroxyfatty acids (FAHFAs). As expected, MDA concentrations were the lowest in group K. Our findings can better explain ongoing pathologies, both acute and chronic, with the potential for future diagnosis and treatment.