Project description:The goal of these studies was to delineate mechanisms of crosstalk between the atherosclerotic arterial wall of the aorta and the peripheral nervous system (PNS) in aged hyperlipidemic ApoE-deficient mice. We had observed by immunohistochemistry and morphometry that axon density of the PNS in adventitia segments that were located adjacent to advanced atherosclerotic plaques of aged hyperlipidemic ApoE-deficient mice were markedly higher than those adventitia segments that did not show adjacent atherosclerotic plaques in the intima layer. It is noteworthy in this connection that neither the media nor the intimal layer are innervated by axon endings. However, the adventitia layer of arteries is a conduit for axons and nerves of the PNS connecting the peripheral ganglia and peripheral organs including the spleen. In addition, we discovered (see references below) that atherosclerosis is sensed by the immune system of aged ApoE-deficient mice resulting in the formation of artery tertiary lymphoid organs in the adventitia layer of the arterial wall. To examine potential molecular mechanisms of the crosstalk between the disease aorta and the PNS, we isolated adventitia tissues and media tissues from aortas of ApoE-deficient mice and used wild-type mice as controls. Moreover, we observed that the sympathetic nervous system paraaortic and periaortic ganglia in aged ApoE-deficient but not of aged wild-type mice were infiltrated by leukocytes indicating that atherosclerosis is associated with major alterations of the PNS including axonogenesis and ganglionitis. To identify potential molecules involved in the crosstalk, we isolated respective tissues (media, adventitia, ganglia) by laser capture microdissection and generated large scale mRNA expression arrays to construct transcript maps that were assembled into transcript atlases. Publications related to this approach: Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors. Hu D, Mohanta SK, Yin C, Peng L, Ma Z, Srikakulapu P, Grassia G, MacRitchie N, Dever G, Gordon P, Burton FL, Ialenti A, Sabir SR, McInnes IB, Brewer JM, Garside P, Weber C, Lehmann T, Teupser D, Habenicht L, Beer M, Grabner R, Maffia P, Weih F, Habenicht AJ. Immunity. 2015 Jun 16;42(6):1100-15. doi: 10.1016/j.immuni.2015.05.015. Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis. Mohanta SK, Yin C, Peng L, Srikakulapu P, Bontha V, Hu D, Weih F, Weber C, Gerdes N, Habenicht AJ. Circ Res. 2014 May 23;114(11):1772-87. doi: 10.1161/CIRCRESAHA.114.301137. Review. Control of dichotomic innate and adaptive immune responses by artery tertiary lymphoid organs in atherosclerosis. Weih F, Gräbner R, Hu D, Beer M, Habenicht AJ. Front Physiol. 2012 Jul 6;3:226. doi: 10.3389/fphys.2012.00226. Laser-capture microdissection of hyperlipidemic/ApoE⁻/⁻ mouse aorta atherosclerosis. Beer M, Doepping S, Hildner M, Weber G, Grabner R, Hu D, Mohanta SK, Srikakulapu P, Weih F, Habenicht AJ. Methods Mol Biol. 2011;755:417-28. doi: 10.1007/978-1-61779-163-5_35. apoE-Adventitia arrays were submitted previously (GSM252007, GSM252008, GSM252009, GSM252010, GSM252011, GSM252014, GSM252015, GSM252016; GSE10000, GSE40156) and are now submitted together with new wild-type adventitia arrays not previously published in order to make all adventitia of ApoE-deficient mice and wild-type mice available in one new submission/location.

Project description:The goal of these studies was to delineate mechanisms of crosstalk between the atherosclerotic arterial wall of the aorta and the peripheral nervous system (PNS) in aged hyperlipidemic ApoE-deficient mice. We had observed by immunohistochemistry and morphometry that axon density of the PNS in adventitia segments that were located adjacent to advanced atherosclerotic plaques of aged hyperlipidemic ApoE-deficient mice were markedly higher than those adventitia segments that did not show adjacent atherosclerotic plaques in the intima layer. It is noteworthy in this connection that neither the media nor the intimal layer are innervated by axon endings. However, the adventitia layer of arteries is a conduit for axons and nerves of the PNS connecting the peripheral ganglia and peripheral organs including the spleen. In addition, we discovered (see references below) that atherosclerosis is sensed by the immune system of aged ApoE-deficient mice resulting in the formation of artery tertiary lymphoid organs in the adventitia layer of the arterial wall. To examine potential molecular mechanisms of the crosstalk between the disease aorta and the PNS, we isolated adventitia tissues and media tissues from aortas of ApoE-deficient mice and used wild-type mice as controls. Moreover, we observed that the sympathetic nervous system paraaortic and periaortic ganglia in aged ApoE-deficient but not of aged wild-type mice were infiltrated by leukocytes indicating that atherosclerosis is associated with major alterations of the PNS including axonogenesis and ganglionitis. To identify potential molecules involved in the crosstalk, we isolated respective tissues (media, adventitia, ganglia) by laser capture microdissection and generated large scale mRNA expression arrays to construct transcript maps that were assembled into transcript atlases. Publications related to this approach: Artery Tertiary Lymphoid Organs Control Aorta Immunity and Protect against Atherosclerosis via Vascular Smooth Muscle Cell Lymphotoxin β Receptors. Hu D, Mohanta SK, Yin C, Peng L, Ma Z, Srikakulapu P, Grassia G, MacRitchie N, Dever G, Gordon P, Burton FL, Ialenti A, Sabir SR, McInnes IB, Brewer JM, Garside P, Weber C, Lehmann T, Teupser D, Habenicht L, Beer M, Grabner R, Maffia P, Weih F, Habenicht AJ. Immunity. 2015 Jun 16;42(6):1100-15. doi: 10.1016/j.immuni.2015.05.015. Artery tertiary lymphoid organs contribute to innate and adaptive immune responses in advanced mouse atherosclerosis. Mohanta SK, Yin C, Peng L, Srikakulapu P, Bontha V, Hu D, Weih F, Weber C, Gerdes N, Habenicht AJ. Circ Res. 2014 May 23;114(11):1772-87. doi: 10.1161/CIRCRESAHA.114.301137. Review. Control of dichotomic innate and adaptive immune responses by artery tertiary lymphoid organs in atherosclerosis. Weih F, Gräbner R, Hu D, Beer M, Habenicht AJ. Front Physiol. 2012 Jul 6;3:226. doi: 10.3389/fphys.2012.00226. Laser-capture microdissection of hyperlipidemic/ApoE⁻/⁻ mouse aorta atherosclerosis. Beer M, Doepping S, Hildner M, Weber G, Grabner R, Hu D, Mohanta SK, Srikakulapu P, Weih F, Habenicht AJ. Methods Mol Biol. 2011;755:417-28. doi: 10.1007/978-1-61779-163-5_35.

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Crosstalk between the diseased atherosclerotic aorta and the peripheral nervous system

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