Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis
BACKGROUND: Disease of the aorta varies from atherosclerosis to aneurysms with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience.
METHODS: Intimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.
RESULTS: Non-hemorrhagic, non atheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation.
CONCLUSION: These findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function but even together are not sufficient to induce atherosclerosis.
FUNDING: R01-HL146723, R01-HL168473, and Yale Department of Surgery.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
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Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
JCI insight - (2024) vom: 09. Apr. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hassab, Abdulrahman Hm [VerfasserIn] |
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Date Revised 09.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1172/jci.insight.172437 |
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| funding: |
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| PPN (Katalog-ID): |
NLM37082153X |
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| 100 | 1 | |a Hassab, Abdulrahman Hm |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Intimomedial tears of the aorta heal by smooth muscle cell-mediated fibrosis without atherosclerosis |
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| 500 | |a Date Revised 09.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status Publisher | ||
| 520 | |a BACKGROUND: Disease of the aorta varies from atherosclerosis to aneurysms with complications including rupture, dissection, and poorly characterized limited tears. We studied limited tears without any mural hematoma, termed intimomedial tears to gain insight into aortic vulnerability to excessive wall stresses. Our premise is that minimal injuries in aortas with sufficient medial resilience to prevent tear progression correspond to initial mechanisms leading to complete structural failure in aortas with significantly compromised medial resilience | ||
| 520 | |a METHODS: Intimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy | ||
| 520 | |a RESULTS: Non-hemorrhagic, non atheromatous tears correlated with advanced aneurysmal disease and most lacked distinctive symptoms or radiological signs. Tears traversed the intima and part of the subjacent media, while the resultant defects were partially or completely filled with neointima characterized by differentiated smooth muscle cells, scattered leukocytes, dense fibrosis, and absent elastic laminae despite tropoelastin synthesis. Healed lesions contained organized fibrin at tear edges without evidence of plasma and erythrocyte extravasation or lipid accumulation | ||
| 520 | |a CONCLUSION: These findings suggest a multiphasic model of aortic wall failure in which primary lesions of intimomedial tears either heal if the media is sufficiently resilient or progress as dissection or rupture by medial delamination and tear completion, respectively. Moreover, mural incorporation of thrombus and cellular responses to injury, two historically important concepts in atheroma pathogenesis, contribute to vessel wall repair with adequate conduit function but even together are not sufficient to induce atherosclerosis | ||
| 520 | |a FUNDING: R01-HL146723, R01-HL168473, and Yale Department of Surgery | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Atherosclerosis | |
| 650 | 4 | |a Vascular biology | |
| 700 | 1 | |a Hur, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Vallabhajosyula, Prashanth |e verfasserin |4 aut | |
| 700 | 1 | |a Tellides, George |e verfasserin |4 aut | |
| 700 | 1 | |a Assi, Roland |e verfasserin |4 aut | |
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