MO_V_L: Molecular Sciences V. Lectures
Introduction:
Lymphatic vessels are present in the arterial wall, but the 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.
Aim:
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 were tissue cleared, followed by immunostaining. In parallel, Ldlr -/- and ApoE-/- mice on control or high-fat diet were used to characterize the lymphatic vasculature in atherosclerosis by whole aorta stainings and paraffin-based histology followed by immunostainings. To investigate if lymphangiogenesis has an impact on the development of atherosclerosis, we used ApoE-/- mice with a conditional deletion of a lymphangiogenic factor.
Results:
We could demonstrate that lymphatic vessels are present in the adventitia of the aorta. Both Ldlr -/- and ApoE-/- mice developed severe atherosclerosis on high-fat diet, indicating the largest plaques in the aortic arch. Atherosclerotic mice showed an increased number of lymphatic vessels in the arterial wall as well as changes in the morphology of those vessels. Experiments with ApoE-/- mice with a deleted lymphangiogenic factor showed that female mice develop more calcification in the aortic arch.
Conclusion:
Our results suggest the possible role of the lymphatic vasculature in the development of atherosclerosis. Defining the role of the lymphatic system in the pathogenesis of atherosclerosis may lead to the development of novel therapeutic approaches in the future.
Funding:
This work was supported by the National Research, Development and Innovation Office (NVKP_16-2016-1-0039 to Z.J.), the European Union, the Hungarian Government (VEKOP2.3.2-16-2016-00002) and the Higher Education Institutional Excellence Program of the Ministry for Innovation and Technology in Hungary, within the framework of the Molecular Biology thematic program of the Semmelweis University.
Semmelweis University, Doctoral School of Molecular Medicine