Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease
Popliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, pa...
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MDPI AG
2023-07-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/7/1074 |
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| author | Jessica Pauli Tessa Reisenauer Greg Winski Nadja Sachs Ekaterina Chernogubova Hannah Freytag Christoph Otto Christian Reeps Hans-Henning Eckstein Claus-Jürgen Scholz Lars Maegdefessel Albert Busch |
| author_facet | Jessica Pauli Tessa Reisenauer Greg Winski Nadja Sachs Ekaterina Chernogubova Hannah Freytag Christoph Otto Christian Reeps Hans-Henning Eckstein Claus-Jürgen Scholz Lars Maegdefessel Albert Busch |
| author_sort | Jessica Pauli |
| collection | DOAJ |
| description | Popliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, partially from the same patients, were analyzed by immunohistochemistry, fluorescence imaging, Affymetrix mRNA expression profiling, qPCR and OLink proteomics, and compared to atherosclerotic (<i>n</i> = 6) and abdominal aortic aneurysm (AAA) tissue (<i>n</i> = 19). Additionally, primary cell culture of PAA-derived vascular smooth muscle cells (VSMC) was established for modulation and growth analysis. Compared to non-aneurysmatic popliteal arteries, VSMCs lose the contractile phenotype and the cell proliferation rate increases significantly in PAA. Array analysis identified APOE higher expressed in PAA samples, co-localizing with VSMCs. APOE stimulation of primary human PAA VSMCs significantly reduced cell proliferation. Accordingly, contractile VSMC markers were significantly upregulated. A single case of osseous mechanically induced PAA with a non-diseased VSMC profile emphasizes these findings. Carefully concluded, PAA pathogenesis shows similar features to AAA, yet the mechanisms involved might differ. APOE is specifically higher expressed in PAA tissue and could be involved in VSMC phenotype rescue. |
| first_indexed | 2024-03-11T01:15:33Z |
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| id | doaj.art-5a3b4a3811d74ba8b281dfc798a1ae6e |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-11T01:15:33Z |
| publishDate | 2023-07-01 |
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| series | Biomolecules |
| spelling | doaj.art-5a3b4a3811d74ba8b281dfc798a1ae6e2023-11-18T18:31:03ZengMDPI AGBiomolecules2218-273X2023-07-01137107410.3390/biom13071074Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm DiseaseJessica Pauli0Tessa Reisenauer1Greg Winski2Nadja Sachs3Ekaterina Chernogubova4Hannah Freytag5Christoph Otto6Christian Reeps7Hans-Henning Eckstein8Claus-Jürgen Scholz9Lars Maegdefessel10Albert Busch11Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyMolecular Vascular Medicine Group, Center for Molecular Medicine, Karolinska Institute, 17177 Stockholm, SwedenDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyMolecular Vascular Medicine Group, Center for Molecular Medicine, Karolinska Institute, 17177 Stockholm, SwedenDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyDepartment of General, Visceral, Transplantation, Vascular & Pediatric Surgery, University Hospital Würzburg, 97080 Würzburg, GermanyDivision of Vascular and Endovascular Surgery, Department for Visceral, Thoracic and Vascular Surgery, Medical Faculty Carl Gustav Carus and University Hospital, Technische Universität Dresden, 01307 Dresden, GermanyDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyWisplinghoff Laboratories, 50858 Cologne, GermanyDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyDepartment for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, 81675 Munich, GermanyPopliteal artery aneurysm (PAA) is the most frequent peripheral aneurysm, primarily seen in male smokers with a prevalence below 1%. This exploratory study aims to shed light on cellular mechanisms involved in PAA progression. Sixteen human PAA and eight non-aneurysmatic popliteal artery samples, partially from the same patients, were analyzed by immunohistochemistry, fluorescence imaging, Affymetrix mRNA expression profiling, qPCR and OLink proteomics, and compared to atherosclerotic (<i>n</i> = 6) and abdominal aortic aneurysm (AAA) tissue (<i>n</i> = 19). Additionally, primary cell culture of PAA-derived vascular smooth muscle cells (VSMC) was established for modulation and growth analysis. Compared to non-aneurysmatic popliteal arteries, VSMCs lose the contractile phenotype and the cell proliferation rate increases significantly in PAA. Array analysis identified APOE higher expressed in PAA samples, co-localizing with VSMCs. APOE stimulation of primary human PAA VSMCs significantly reduced cell proliferation. Accordingly, contractile VSMC markers were significantly upregulated. A single case of osseous mechanically induced PAA with a non-diseased VSMC profile emphasizes these findings. Carefully concluded, PAA pathogenesis shows similar features to AAA, yet the mechanisms involved might differ. APOE is specifically higher expressed in PAA tissue and could be involved in VSMC phenotype rescue.https://www.mdpi.com/2218-273X/13/7/1074popliteal artery aneurysmapolipoprotein Evascular smooth muscle cellphenotype switchproliferation |
| spellingShingle | Jessica Pauli Tessa Reisenauer Greg Winski Nadja Sachs Ekaterina Chernogubova Hannah Freytag Christoph Otto Christian Reeps Hans-Henning Eckstein Claus-Jürgen Scholz Lars Maegdefessel Albert Busch Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease Biomolecules popliteal artery aneurysm apolipoprotein E vascular smooth muscle cell phenotype switch proliferation |
| title | Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease |
| title_full | Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease |
| title_fullStr | Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease |
| title_full_unstemmed | Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease |
| title_short | Apolipoprotein E (ApoE) Rescues the Contractile Smooth Muscle Cell Phenotype in Popliteal Artery Aneurysm Disease |
| title_sort | apolipoprotein e apoe rescues the contractile smooth muscle cell phenotype in popliteal artery aneurysm disease |
| topic | popliteal artery aneurysm apolipoprotein E vascular smooth muscle cell phenotype switch proliferation |
| url | https://www.mdpi.com/2218-273X/13/7/1074 |
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