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Intimomedial tears of the aorta heal by smooth muscle cell–mediated fibrosis without atherosclerosis
Abdulrahman H.M. Hassab, … , George Tellides, Roland Assi
Abdulrahman H.M. Hassab, … , George Tellides, Roland Assi
Published April 9, 2024
Citation Information: JCI Insight. 2024;9(9):e172437. https://doi.org/10.1172/jci.insight.172437.
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Clinical Research and Public Health Vascular biology

Intimomedial tears of the aorta heal by smooth muscle cell–mediated fibrosis without atherosclerosis

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Abstract

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 Nonhemorrhagic, nonatheromatous 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 NIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.

Authors

Abdulrahman H.M. Hassab, David J. Hur, Prashanth Vallabhajosyula, George Tellides, Roland Assi

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Figure 4

Cell types in intimomedial tears.

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Cell types in intimomedial tears.
Aortas with intimomedial tears were an...
Aortas with intimomedial tears were analyzed by immunofluorescence confocal microscopy. (A) The endothelial cell marker CD31 (red) is detected on the luminal surface of both distant aorta and tear neointima without evidence of mural neovascularization. (B) The SMC marker SMA (red) is detected in most cells of the distant media and tear neointima. Distant media cells are spindle shaped and circumferentially oriented, whereas tear neointima cells are smaller and irregularly shaped. Scattered CD45+ leukocytes (white) are detected in the tear neointima, but not distant media. (C) SMA+ SMCs of uniform size and shape are the exclusive constituents of the distant media and tear base, while the fibroblast product decorin (green) is restricted to the adventitia where single layers of SMCs support occasional microvessels. In addition to DAPI staining nucleic DNA (blue) indicating cell density and orientation, autofluorescence (less intense blue) of elastic laminae is detected in the distant media and tear base, but not the tear neointima. Orientation: internal aspect above, external aspect below. N, neointima; M, media; A, adventitia. Scale bars: 25 μm.

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