Carolin Christ1,2 and Zoltán Jakus1,2
1 Department of Physiology, Semmelweis University School of Medicine, Budapest, Hungary
2 MTA-SE „Lendület” Lymphatic Physiology Research Group of the Hungarian Academy of Sciences and the Semmelweis University, Budapest, Hungary
Lymphatic vessels are present in the arterial wall, but the physiological and pathophysiological role of these vessels is not fully understood yet. Recently it has been shown that lymphatic vessels participate in reverse cholesterol transport, suggesting a possible role in the development of atherosclerosis.
In this study we aimed to characterize the morphology and growth of the lymphatic vasculature in atherosclerosis.
Materials and Methods:
To visualize lymphatic vessels in the arterial wall, whole aortas of lymphatic reporter mice were cleared by a tissue clearing method, followed by whole mount immunostaining. In parallel, Ldlr -/- and ApoE-/- mice on control or high-fat diet were used to characterize the lymphatic morphology and growth in atherosclerosis. The lymphatic vasculature and plaque formation in atherosclerosis was analyzed by paraffin-based histology followed by H/E-, Oil-Red-O- and immunostaining of lymphatic endothelial markers.
We demonstrated the presence of several lymphatic vessels in the adventitia of the thoracic and lumbar aorta but less lymphatic structures in the aortic arch. Both Ldlr -/- and ApoE-/- mice developed severe atherosclerosis on a high-fat diet, indicating the largest atherosclerotic plaques in the aortic arch. Atherosclerotic mice showed an increased number of lymphatic vessels in the adventitia of the arterial wall in comparison to mice on control diet.
Our results suggest the possible role of the lymphatic vasculature in the development of atherosclerosis. In current experiments we are using genetic loss of function and gain of function approaches to block and stimulate lymphatic growth in atherosclerotic mice. Defining the role of the lymphatic system in the pathogenesis of atherosclerosis may lead to the development of novel therapeutic approaches in the future.
Doctoral School: Molecular Medicine
Program: Cellular and Molecular Physiology
Supervisor: Zoltán Jakus
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