Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients

Grewal, Nimrat; Girdauskas, Evaldas; Idhrees, Mohammed; Velayudhan, Bashi; Klautz, Robert J.M.; Driessen, Antoine H.G.; Poelmann, Robert E.

doi:10.1016/j.carpath.2022.107478

Cited by 14 publications

(17 citation statements)

References 21 publications

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“…This finding has been reported by others, as well. 14 Grewal and colleagues 19 further characterized the aortic wall in patients with BAVs and found a vascular smooth muscle differentiation defect in ascending aorta with BAVs before the development of medial degenerative changes and aneurysm formation. 19 They described a significantly thinner intimal layer without features of atherosclerosis ( P < .001) and a significantly thicker medial layer ( P < .001) with more MEMA ( P < .001) in nondilated ascending aortic walls with BAVs than in aortic walls with TAVs.…”

Section: Discussionmentioning

confidence: 99%

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections

Buja,

Zhao,

Sadaf

et al. 2024

Texas Heart Institute Journal

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Objective The purpose of this study was to apply contemporary consensus criteria developed by the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology to the evaluation of aortic pathology, with the expectation that the additional pathologic information may enhance the understanding and management of aortic diseases. Methods A scoring system was applied to ascending aortic specimens from 42 patients with heritable thoracic aortic disease and known genetic variations and from 86 patients from a single year, including patients with known genetic variations (n = 12) and patients with sporadic disease (n = 74). Results The various types of lesions of medial degeneration and the overall severity of medial degeneration overlapped considerably between those patients with heritable disease and those with sporadic disease; however, patients with heritable thoracic aortic disease had significantly more overall medial degeneration (P = .004) and higher levels of elastic fiber fragmentation (P = .03) and mucoid extracellular matrix accumulation (P = .04) than patients with sporadic thoracic aortic disease. Heritable thoracic aortic disease with known genetic variation was more prevalent in women than in men (27.2% vs 9.8%; P = .04), and women had more severe medial degeneration than men (P = .04). Medial degeneration scores were significantly lower for patients with bicuspid aortic valves than for patients with tricuspid aortic valves (P = .03). Conclusion The study’s findings indicate considerable overlap in the pattern, extent, and severity of medial degeneration between sporadic and hereditary types of thoracic aortic disease. This finding suggests that histopathologic medial degeneration represents the final common outcome of diverse pathogenetic factors and mechanisms.

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Section: Discussionmentioning

confidence: 99%

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections

Buja,

Zhao,

Sadaf

et al. 2024

Texas Heart Institute Journal

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“…It has earlier been concluded that even though both the intimal and adventitial layers contribute to the disease process ( 22 ), progressive mechanical weakening of the aorta is mainly caused by degeneration of the medial layer, regardless of the etiology ( 14 , 23 – 25 ). In the current study, medial pathology was also worse as compared to the intimal and adventitial layer in all aortopathy patients.…”

Section: Discussionmentioning

confidence: 99%

“…The degradation of the extracellular matrix can result in the activation of several signaling pathways which in turn leads to medial degeneration and progressive weakening of the vessel wall ( 30 ). The phenotypic switch is triggered by inflammation and vascular injury ( 29 , 31 – 33 ). The local environmental factors that modulate vascular smooth muscle cell phenotype include growth factors, such as platelet-derived growth factor ( 34 , 35 ) and TGF-β ( 34 , 36 ), angiotensin II ( 37 ), nitric oxide ( 34 ), reactive oxygen species ( 38 ), and other components of the ECM.…”

Section: Discussionmentioning

confidence: 99%

Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease

Grewal

Dolmaci²,

Jansen³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundThoracic aortopathy is a serious complication which is more often seen in patients with Marfan syndrome (MFS) and patients with a bicuspid aortic valve (BAV) than in individuals with a tricuspid aortic valve (TAV). The identification of common pathological mechanisms leading to aortic complications in non-syndromic and syndromic diseases would significantly improve the field of personalized medicine.ObjectiveThis study sought to compare thoracic aortopathy between MFS, BAV, and TAV individuals.Materials and methodsBicuspid aortic valve (BAV; n = 36), TAV (n = 23), and MFS (n = 8) patients were included. Ascending aortic wall specimen were studied for general histologic features, apoptosis, markers of cardiovascular ageing, expression of synthetic and contractile vascular smooth muscle cells (VSMC), and fibrillin-1 expression.ResultsThe MFS group showed many similarities with the dilated BAV. Both patient groups showed a thinner intima (p < 0.0005), a lower expression of contractile VSMCs (p < 0.05), more elastic fiber thinning (p < 0.001), lack of inflammation (p < 0.001), and a decreased progerin expression (p < 0.05) as compared to the TAV. Other features of cardiovascular ageing differed between the BAV and MFS. Dilated BAV patients demonstrated less medial degeneration (p < 0.0001), VSMC nuclei loss (p < 0.0001), apoptosis of the vessel wall (p < 0.03), and elastic fiber fragmentation and disorganization (p < 0.001), as compared to the MFS and dilated TAV.ConclusionThis study showed important similarities in the pathogenesis of thoracic aortic aneurysms in BAV and MFS. These common mechanisms can be further investigated to personalize treatment strategies in non-syndromic and syndromic conditions.

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“…The majority of these studies did not show significant differences in immune cell numbers between non- and dilated aortas of patients with a BAV. Moreover, many BAV aorta aneurysms appear normal in terms of media matrix composition including lack of cystic medial degeneration ( 44 , 45 ). Yet, other studies described neovascularization and low grade inflammation in aneurysmatic and dissected BAV aortas ( 23 , 25 ).…”

Section: Discussionmentioning

confidence: 99%

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve

Staal

Cortenbach²,

Gorris³

et al. 2023

Front. Cardiovasc. Med.

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BackgroundBicuspid aortic valve (BAV) is associated with ascending aorta aneurysms and dissections. Presently, genetic factors and pathological flow patterns are considered responsible for aneurysm formation in BAV while the exact role of inflammatory processes remains unknown.MethodsIn order to objectify inflammation, we employ a highly sensitive, quantitative immunohistochemistry approach. Whole slides of dissected, dilated and non-dilated ascending aortas from BAV patients were quantitatively analyzed.ResultsDilated aortas show a 4-fold increase of lymphocytes and a 25-fold increase in B lymphocytes in the adventitia compared to non-dilated aortas. Tertiary lymphoid structures with B cell follicles and helper T cell expansion were identified in dilated and dissected aortas. Dilated aortas were associated with an increase in M1-like macrophages in the aorta media, in contrast the number of M2-like macrophages did not change significantly.ConclusionThis study finds unexpected large numbers of immune cells in dilating aortas of BAV patients. These findings raise the question whether immune cells in BAV aortopathy are innocent bystanders or contribute to the deterioration of the aortic wall.

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Structural abnormalities in the non-dilated ascending aortic wall of bicuspid aortic valve patients

Cited by 14 publications

References 21 publications

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections

Insights From the Histopathologic Analysis of Acquired and Genetic Thoracic Aortic Aneurysms and Dissections

Thoracic aortopathy in Marfan syndrome overlaps with mechanisms seen in bicuspid aortic valve disease

Adventitial adaptive immune cells are associated with ascending aortic dilatation in patients with a bicuspid aortic valve

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