Potential Molecular Pathways Related to Pulmonary Artery Aneurysm Development: Lessons to Learn from the Aorta

Nuche, Jorge; Palomino-Doza, Julián; Arribas, Fernando; Delgado, Juan; Ibáñez, Borja; Oliver, Eduardo; Escribano, Pilar

doi:10.3390/ijms21072509

Cited by 9 publications

(13 citation statements)

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“…In addition, osseous metaplasia (arrowhead) was observed close to the cholesterol clefts. d The cholesterol granuloma was adjacent to the remnants of the thymic tissue with the presence of Hassall's corpuscles (large arrow) different segments of the aorta [14]. The pathological findings in our patient showed cholesterol clefts surrounded by inflammatory infiltrates, histocytes, and multinucleated giant cells, some of which had phagocytosed hemosiderin granules.…”

Section: Discussionmentioning

confidence: 66%

“…High levels of low-density lipoprotein cholesterol and triglyceride levels lead to atherosclerosis, which causes weakening of the aortic wall and results in the development of aneurysms. Around 10% of patients diagnosed with aortic aneurysm have multiple aneurysms in different segments of the aorta [ 14 ]. The pathological findings in our patient showed cholesterol clefts surrounded by inflammatory infiltrates, histocytes, and multinucleated giant cells, some of which had phagocytosed hemosiderin granules.…”

Section: Discussionmentioning

confidence: 99%

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Multifocal cholesterol granulomas of the anterior mediastinum

2020

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Background: Cholesterol granuloma in the mediastinum is rarely observed, accounting for 1% of all mediastinum tumors. There have been only a few reports of multifocal cholesterol granulomas of the thymus. We herein report a rare case of multifocal cholesterol granuloma in the thymus that was incidentally detected during follow-up of an aortic aneurysm. Case presentation: The patient was a 70-year-old man with dyslipidemia and hypertension who was referred to our hospital to undergo an operation for chest aortic aneurysm. Preoperative computed tomography (CT) showed 4 lesions in the anterior mediastinum measuring up to 4 cm in size with slight contrast enhancement and spotty calcification. Therefore, a thymoma, bronchogenic cyst, or lymphangioma were considered as the preoperative diagnosis. The patient underwent total thymectomy under thoracotomy followed by aortic arch replacement for the aortic aneurysm. The pathological diagnosis was multifocal cholesterol granulomas in the thymus. Conclusions: Cholesterol granulomas should be included in the differential diagnosis of cystic tumor in the mediastinum, especially in patients with basal disease such as dyslipidemia and hypertension, which may lead to aortic aneurysm. Furthermore, complete surgical resection and a detailed histological evaluation are important for the accurate diagnosis and treatment.

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Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Multifocal cholesterol granulomas of the anterior mediastinum

2020

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“…Increased adventitial collagen is observed in all autograft samples acquired at reoperation and in all animal studies, suggesting a common mode of remodeling in both failed and well-adapted autografts. This form of ECM remodeling is a crucial part of arterial homeostasis in arterial aging, pulmonary arterial hypertension and aneurysm development ( 27 , 129 , 130 ). Elevated myofibroblast, MMP1, MMP13 and TGF-β levels are seen in clinical autograft explants at over 10 years post-operatively ( 24 , 25 , 30 , 109 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the general population, pulmonary artery aneurysm is a rare entity, reported only 8 times in 109,571 autopsies and mainly associated with pulmonary arterial hypertension in the setting of congenital heart disease ( 130 , 137 ). There are yet several molecular pathways implied in thoracic aortic aneurysms which are also involved in the development of pulmonary arterial hypertension and pulmonary artery aneurysm.…”

Section: Discussionmentioning

confidence: 99%

Understanding Pulmonary Autograft Remodeling After the Ross Procedure: Stick to the Facts

Hoof

Verbrugghe

Jones

et al. 2022

Front. Cardiovasc. Med.

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The Ross, or pulmonary autograft, procedure presents a fascinating mechanobiological scenario. Due to the common embryological origin of the aortic and pulmonary root, the conotruncus, several authors have hypothesized that a pulmonary autograft has the innate potential to remodel into an aortic phenotype once exposed to systemic conditions. Most of our understanding of pulmonary autograft mechanobiology stems from the remodeling observed in the arterial wall, rather than the valve, simply because there have been many opportunities to study the walls of dilated autografts explanted at reoperation. While previous histological studies provided important clues on autograft adaptation, a comprehensive understanding of its determinants and underlying mechanisms is needed so that the Ross procedure can become a widely accepted aortic valve substitute in select patients. It is clear that protecting the autograft during the early adaptation phase is crucial to avoid initiating a sequence of pathological remodeling. External support in the freestanding Ross procedure should aim to prevent dilatation while simultaneously promoting remodeling, rather than preventing dilatation at the cost of vascular atrophy. To define the optimal mechanical properties and geometry for external support, the ideal conditions for autograft remodeling and the timeline of mechanical adaptation must be determined. We aimed to rigorously review pulmonary autograft remodeling after the Ross procedure. Starting from the developmental, microstructural and biomechanical differences between the pulmonary artery and aorta, we review autograft mechanobiology in relation to distinct clinical failure mechanisms while aiming to identify unmet clinical needs, gaps in current knowledge and areas for further research. By correlating clinical and experimental observations of autograft remodeling with established principles in cardiovascular mechanobiology, we aim to present an up-to-date overview of all factors involved in extracellular matrix remodeling, their interactions and potential underlying molecular mechanisms.

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“…Activated neutrophils form neutrophil extracellular traps (NETs), propagating the inflammatory reactions and culminating in eventual AAA ( 56 ). Neutrophils are also known to secrete ECM-degrading collagenases such as MMP-8 and certain proteases ( 66 ). In angiotensin II-lysyl oxidase inhibitor ( β- Aminopropionitrile monofumarate; BAPN)–preconditioned aortic dissection model mice, adventitial neutrophil recruitment and activation were detected.…”

Section: Kp Regulation In Different Cell Typesmentioning

confidence: 99%

Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases

et al. 2021

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Aortic diseases are the primary public health concern. As asymptomatic diseases, abdominal aortic aneurysm (AAA) and atherosclerosis are associated with high morbidity and mortality. The inflammatory process constitutes an essential part of a pathogenic cascade of aortic diseases, including atherosclerosis and aortic aneurysms. Inflammation on various vascular beds, including endothelium, smooth muscle cell proliferation and migration, and inflammatory cell infiltration (monocytes, macrophages, neutrophils, etc.), play critical roles in the initiation and progression of aortic diseases. The tryptophan (Trp) metabolism or kynurenine pathway (KP) is the primary way of degrading Trp in most mammalian cells, disturbed by cytokines under various stress. KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), etc. Depends on the cell types, these metabolites can elicit both hyper- and anti-inflammatory effects. Accumulating evidence obtained from various animal disease models indicates that KP contributes to the inflammatory process during the development of vascular disease, notably atherosclerosis and aneurysm development. This review outlines current insights into how perturbed Trp metabolism instigates aortic inflammation and aortic disease phenotypes. We also briefly highlight how targeting Trp metabolic pathways should be considered for treating aortic diseases.

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Potential Molecular Pathways Related to Pulmonary Artery Aneurysm Development: Lessons to Learn from the Aorta

Cited by 9 publications

References 93 publications

Multifocal cholesterol granulomas of the anterior mediastinum

Multifocal cholesterol granulomas of the anterior mediastinum

Understanding Pulmonary Autograft Remodeling After the Ross Procedure: Stick to the Facts

Tryptophan Catabolism and Inflammation: A Novel Therapeutic Target For Aortic Diseases

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