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dc.rights.licenseCC-BY-NC-ND
dc.contributor.advisorMokry, Michal
dc.contributor.authorWolters, Bibi
dc.date.accessioned2024-10-31T01:02:54Z
dc.date.available2024-10-31T01:02:54Z
dc.date.issued2024
dc.identifier.urihttps://studenttheses.uu.nl/handle/20.500.12932/48054
dc.description.abstractBackground & objectives Atherosclerotic plaques within arteries are a major risk factor for ischemic events, imposing significant global health and economic burdens. Research suggests that histological and molecular characteristics of plaques can be predictive of future cardiovascular events. Identification of non-invasive serum biomarkers for these plaque characteristics would enhance patient risk stratification and treatment optimization. The concept of non-invasive serum biomarkers assumes similarity of histological and molecular characteristics exists between the plaques within an individual. This study aims to determine the validity of this concept by assessing the concordance of histological and molecular characteristics among atherosclerotic plaques in individuals. By doing so, we aim to provide additional insights into atherosclerosis as a systemic disease, and thus confirm or reject the potential of non-invasive plasma derived biomarkers for plaque characteristics and risk stratification. Methods We employed the Athero-Express biobank to select patients who had undergone multiple endarterectomies for non-restenotic plaques from carotid and femoral arteries. Patients were grouped by the artery from which the plaques were obtained: carotid-carotid pairs, femoral-femoral pairs, and carotid-femoral and femoral-carotid pairs, depending on the order of plaque sampling. The plaques were graded on the basis of 6 histological characteristics: calcification, collagen, smooth muscle cells (SMC), macrophages, fat and intraplaque hemorrhage (IPH); histologically phenotyped as atheromatous, fibroatheromatous or fibrous plaques; and subjected to transcriptomic sequencing. For each plaque group and each plaque pair within it, we compared the concordance of histological characteristics and histological phenotypes, using permutation tests to assess statistical significance. Concordance of molecular characteristics was evaluated in the carotid-carotid group only. We selected 23 molecular phenotype-defining genes and performed a correlation analysis to determine the degree to which the expression levels of these genes are similar between carotid paired plaques. Results The carotid-carotid pairs were found to exhibit a nominally significant probability of concordance in histological phenotype (p = 0.005), calcification (p = 0.011) and SMC content (p = 0.016). The femoral-femoral pairs were found to exhibit a nominally significant probability of concordance in histological phenotype (p = 0.046), fat content (p = 0.009), and IPH (p = 0.039). No statistically significant probability of concordance was observed for the carotid-femoral and femoral-carotid pairs. Four inflammation-related genes showed a nominally significant, positive correlation between expression levels of carotid-carotid pairs: C1QA (r(33) = .38; p = .026; 95% CI [0.052, 0.632]), CD63 (r(33) = .36; p = .035; 95% CI [0.030, 0.619]), CD74 (r(33) = .41; p = .014; 95% CI [0.092, 0.655]), CXCL12 (r(33) = .38; p = .025; 95% CI [0.053, 0.633]). Conclusions Our findings indicate that paired carotid plaques from the same individual demonstrate a tendency to share similar histological phenotypes, a pattern also observed in paired femoral plaques. Additionally, carotid plaque pairs showed concordance in calcification and SMC content, along with a positive correlation in the expression levels of C1QA, CD63, CD74, and CXCL12. Femoral plaque pairs exhibited concordance in fat content and IPH.
dc.description.sponsorshipUtrecht University
dc.language.isoEN
dc.subjectComparing the histological and molecular characteristics of plaques within individuals
dc.titleAtherosclerotic Plaques within Individuals Exhibit Similarities in Histological Composition and Inflammation-Related Gene Expression
dc.type.contentMaster Thesis
dc.rights.accessrightsOpen Access
dc.subject.courseuuDrug Innovation
dc.thesis.id40700


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