Atherosclerosis | EPFL Graph Search

Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected. The exact cause is not known and is proposed to be multifactorial. Risk factors include abnormal cholesterol levels, elevated levels of inflammatory markers, high blood pressure, diabetes, smoking, obesity, family history, genetic, and an unhealthy diet. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. The narrowing of arteries limits the flow of oxygen-rich blood to parts of the body. Diagnosis i

Impact and implications of mixed plaque class in automated characterization of complex atherosclerotic lesions

Yanan Niu

Atherosclerosis is a complex disease altering vasculature morphology, and subsequently flow, with progressive plaque formation, mural disruption, and lumen occlusion. Determination of clinically-relevant plaque components-particularly calcium, lipid, and fibrous tissue-has driven automated image-based tissue characterization. Atherosclerotic tissue of mixed composition type arises when these principal components interdigitate and combine during the course of progressive atherosclerosis. Nevertheless, such mixed plaque is treated non uniformly, and often neglected, as a distinct class in image analysis. We therefore quantitatively investigate frameworks to characterize mixed and other plaque tissue types, and examine their implications. Convolutional neural networks operated on labeled intravascular optical coherence tomography images using various characterization frameworks. The treatment of mixed plaque by image-based classifiers influenced the accuracy and homogeneity of the segmented classes. Excluding mixed plaque as a class on to itself necessarily assigns heterogeneous lesion subcomponents to one of the three homogeneous subtypes; when included, 61.7% of mixed tissue is labeled as calcium, reducing specificity in homogeneous calcium detection by 34.8%. Segmenting mixed plaque as distinct from homogeneous, non-mixed tissue improves lesion classification. This can be achieved either on the basis of homogeneous tissue classifier prediction uncertainty (77.8% overall accuracy) or by training classifiers to identify mixed plaque as a discrete tissue class (82.9% overall accuracy). Alternatively, mixed plaque can be grouped with one of the homogeneous classes, yielding a single histologically diverse class that helps preserve the homogeneity of the others. Ultimately, the best approach depends upon the alignment of histological and functional distinctions. While no vascular lesion characterization framework or method is universally optimal or appropriate, context should remain central in selecting tissue characterization techniques.

PERGAMON-ELSEVIER SCIENCE LTD2022

Modulation of arginase pathway by hemodynamic forces

Fabienne Riche

It is well recognized that alterations on wall shear stress plays an important role on the development of atherosclerosis disease. It is known that oscillatory shear stress (OSS) flow pattern induces endothelial dysfunction via changes on nitric oxide (NO) pathway. NO is a potent vasodilator molecule and its availability can be evaluated by vasoreactivity organ chamber experiment. Arginase is an enzyme which is implicated in the signaling pathway of NO as it competes with endothelium nitric oxide synthase (eNOS) for the use of arginine. Increase in arginase expression and activity has been associated atherosclerosis, however the modulation of arginase by wall shear stress has never been studied before. This project consists of experimental work to better understand the implication of shear stress, NO and arginase expression in endothelial dysfunction of arteries. By using western blot and immunohistochemistry techniques we investigated the expression and localization of arginase in pig carotid arteries (PCA) perfused in an ex vivo arterial support system. While arginase I isoform was not present in PCA, arginase II was constitutively expressed. Its expression was augmented by exposure to high shear stress (HSS) flow and dependent of flow duration. OSS flow significantly increases the expression of arginase as compared to HSS. Inhibition of arginase in PCA perfused under OSS was not able to improve endothelial function neither NO availability. In a second part we characterize the geometry of rabbit carotid bifurcation and investigate if the receptor-mediated endothelial function and NO availability varies in this bifurcation. In the presence of NOS inhibitor, the contraction of the arteries in response to norepinephirne was higher. This difference is significant for segments which have the better endothelial dependant relaxation: the external carotid and the middle part of the common carotid.

2008

Role of arginase pathway in response to shear stress: new potential therapeutic targets for atherosclerosis?

Rafaela Fernandes Da Silva, Veronica Gambillara, Nikolaos Stergiopulos

Introduction: Alterations of wall shear stress can predispose the endothelium to the development of atherosclerotic plaques. Ample evidence indicates that arginase expression and/or activity correlates with several risk factors for cardiovascular disease including atherosclerosis. However, the role of arginase pathway in response to shear stress has never been investigated. Methods: To evaluate the regulation of arginases by different shear stress patterns without neuroendocrine factors, we perfused carotid arterial segments to the following hemodynamic conditions: unidirectional high and low shear stress, and oscillatory shear stress. After 3 days of flow exposure, vascular function was analyzed by diameter measurements, arginase expression and localization by western blot and immunohistochemistry, respectively. We compared these well-controlled measurements to an in vivo model of shear stress-induced atherogenesis. In brief, the carotid artery of ApoE-/- mice, fed with high cholesterol diet, was exposed to high, low and oscillatory shear stress values by the placement of a shear stress modifier for 9 weeks. Immunohistochemistry was used to determine the expression of arginase I and II and to characterize the arginase expression in different cell types encountered in atherosclerotic plaques. Results: Our preliminary results from ex vivo perfusion arteries showed for the first time that exposure of carotid segments to high shear stress conditions (athero-protective) significantly decrease arginase II protein expression as compared to both low and oscillatory flow conditions. Immunohistochemisty analysis confirmed a pronounced decrease in the expression of arginase II on ECs and SMCs exposed to this high shear stress. Our preliminary data suggest that arginase I and II are also regulated by shear stress in vivo. Arginases were up-regulated on EC, SMC and macrophages of carotid segments exposed either to low stress or to oscillatory shear stress conditions. Conclusions: The present study demonstrates that arginase expression is already modulated by 3 days exposure to different shear stress patterns in carotid arteries perfused ex vivo. Similar findings are also observed in a model of shear stress-induced atherogenesis in vivo. Histopathological analysis of carotid lesions in ApoE-/- mice exposed to shear stress and chronically treated with arginase inhibitors may further elucidate the role of arginases in modulating both plaque size and vulnerability