Department of Surgery (Cardiac), and.
Department of Internal Medicine (Cardiovascular Medicine), Yale School of Medicine, New Haven, Connecticut, USA.
JCI Insight. 2024 Apr 9;9(9):e172437. doi: 10.1172/jci.insight.172437.
BACKGROUNDDisease 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.METHODSIntimomedial tears were macroscopically identified in 9 of 108 ascending aortas after surgery and analyzed by histology and immunofluorescence confocal microscopy.RESULTSNonhemorrhagic, 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.CONCLUSIONThese 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.FUNDINGNIH (R01-HL146723, R01-HL168473) and Yale Department of Surgery.
主动脉疾病的范围从动脉粥样硬化到动脉瘤不等,其并发症包括破裂、夹层和特征不明显的局限性撕裂。我们研究了没有任何壁血肿的局限性撕裂,称为中膜内撕裂,以深入了解主动脉对过度壁应力的脆弱性。我们的前提是,在具有足够中膜弹性以防止撕裂进展的主动脉中,最小的损伤对应于导致中膜弹性明显受损的主动脉完全结构失效的初始机制。
在手术后的 108 个升主动脉中,有 9 个通过组织学和免疫荧光共聚焦显微镜宏观识别出中膜内撕裂,并进行了分析。
非出血性、非动脉粥样硬化性撕裂与晚期动脉瘤性疾病相关,大多数缺乏明显的症状或放射学征象。撕裂穿过内膜并穿透部分下方的中膜,而由此产生的缺陷部分或完全被新生内膜填充,新生内膜的特征是分化的平滑肌细胞、散在的白细胞、致密的纤维化和缺乏弹性层,尽管有原弹性蛋白合成。愈合的病变在撕裂边缘含有有组织的纤维蛋白,没有血浆和红细胞外渗或脂质积累的证据。
这些发现表明主动脉壁衰竭的多相模型,其中中膜内撕裂的原发性病变如果中膜具有足够的弹性,则会愈合,或者分别通过中膜分层和撕裂完成进展为夹层或破裂。此外,血栓的壁内合并和对损伤的细胞反应,这两个在动脉粥样硬化发病机制中具有重要历史意义的概念,有助于具有足够输送功能的血管壁修复,但即使两者结合也不足以引起动脉粥样硬化。
NIH(R01-HL146723,R01-HL168473)和耶鲁大学外科系。