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

TL;DR

The study shows that limited tears in the aorta heal through smooth muscle cell activity and fibrosis without causing atherosclerosis.

Contribution

It reveals a novel healing mechanism for intimomedial tears involving fibrosis and smooth muscle cells, distinct from atherosclerosis.

Findings

Intimomedial tears heal with neointima formation, fibrosis, and absence of hemorrhage or lipid accumulation.

Smooth muscle cell differentiation and fibrin organization are key in healing tears without atherosclerosis.

Tears in resilient aortas heal, while those with compromised media progress to dissection or rupture.

Abstract

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.

Intimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.

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.

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.

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

Smooth muscle cell responses to mechanical injury have a reparative role to prevent the progression of localized vessel wall failure as rupture or dissection.

Figures