Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms

He, Rong; Guo, Dong; Sun, Wei; Papke, Christina L.; Duraisamy, Senthil; Estrera, Anthony L.; Safi, Hazim J.; Ahn, Chul; Buja, L. Maximilian; Arnett, Frank C.; Zhang, Jingwu; Geng, Yong; Milewicz, Dianna M.

doi:10.1016/j.jtcvs.2007.12.063

Cited by 130 publications

(99 citation statements)

References 27 publications

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“…An active participation of both innate/inflammatory and clonotypic responses has been evidenced. Infiltration of inflammatory/immune cells has been actually identified through immune-histochemical assays both in the media and adventitia from aorta samples of patients with sporadic TAA [46,47]. Accordingly, we observed significant increased amounts of CD3 + CD4 + CD8 + CD68 + CD20 + cells in tissue aorta samples from patients with Stanford type A aortic dissection [32].…”

Section: Focus On the Role In Sporadic Taad Of Genetic Variants In Pasupporting

confidence: 48%

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Balistreri

2015

Vascular Pharmacology

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Keywords:Sporadic thoracic aortic aneurysms (TAA) and dissections Genetic variants Biomarkers Targets for new personalized therapeutic treatments Sporadic thoracic aortic aneurysms (TAA) and dissections are one of the major causes of morbidity and mortality worldwide, especially in those older than 65 years. The presentation of TAA is varied and often silent. Thus, sporadic TAA detection is often fortuitous, with identification occurring during a routine physical examination or during an unrelated medical evaluation. Once suspected, confirmation by imaging clinical approaches is needed to allow the choose of the unique treatments for TAA, namely the surgery procedures, including elective surgery or endovascular repair before the onset of catastrophic and fatal complications, such as dissection or rupture. At present, there are no biomarkers available to identify TAAs before visible symptoms. However, recent progresses in understanding of molecular and cellular mechanisms involved in the patho-physiology of sporadic TAA are suggesting different molecular pathways and their genetic variants as potential biomarkers, which might be applied into TAA clinical practice in the near future. Here, we report literature evidence on some disease pathways and their genetic variants on TAA susceptibility and compliances, and their translation as promising TAA preventive and prognostic biomarkers and targets for new personalized therapeutic treatments.

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Section: Focus On the Role In Sporadic Taad Of Genetic Variants In Pasupporting

confidence: 48%

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Balistreri

2015

Vascular Pharmacology

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“…These results show the involvement of the EBP sequence in the stimulation of macrophage chemotaxis in Fbn1 mgR/mgR mice. Macrophage infiltration was also observed in aortic specimens obtained from individuals with Marfan syndrome (He et al 2008). …”

Section: Inflammatory Infiltration Of Immune Cellsmentioning

confidence: 87%

Fibrillin-containing microfibrils are key signal relay stations for cell function

Zeyer

Reinhardt

2015

J. Cell Commun. Signal.

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Fibrillins constitute the backbone of microfibrils in the extracellular matrix of elastic and non-elastic tissues. Mutations in fibrillins are associated with a wide range of connective tissue disorders, the most common is Marfan syndrome. Microfibrils are on one hand important for structural stability in some tissues. On the other hand, microfibrils are increasingly recognized as critical mediators and drivers of cellular signaling. This review focuses on the signaling mechanisms initiated by fibrillins and microfibrils, which are often dysregulated in fibrillin-associated disorders. Fibrillins regulate the storage and bioavailability of growth factors of the TGF-β superfamily. Cells sense microfibrils through integrins and other receptors. Fibrillins potently regulate pathways of the immune response, inflammation and tissue homeostasis. Emerging evidence show the involvement of microRNAs in disorders caused by fibrillin deficiency. A thorough understanding of fibrillinmediated cell signaling pathways will provide important new leads for therapeutic approaches of the underlying disorders.

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“…19) In addition, inflammatory T lymphocytes and macrophages reportedly infiltrate aortic media and adventitia, and those numbers were negatively correlated with patient ages at referral for prophylactic surgical repair, suggesting that inflammation might affect disease progression. 20,21) Dietz and his colleagues performed the most extensive mechanistic studies of these diseases, and identified FBN1 as a causative gene in 1991, 4) with FBN1 mutations accounting for > 60% of MFS patients. FBN1 is a 230 kb gene with 65 exons, and the encoded microfibrillar protein fibrillin-1 contains 7 TGF-β binding protein-like (TB) domains and 47 epidermal growth factor (EGF)-like domains, which are characterized by 8 and 6 conserved cysteine residues that form 4 and 3 intramodule disulfide bonds, respectively.…”

Section: Marfan Syndromementioning

confidence: 99%

Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

et al. 2016

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SummaryMarfan syndrome (MFS) is an autosomal dominant heritable disorder of connective tissue that affects the cardiovascular, skeletal, ocular, pulmonary, and nervous systems and is usually caused by mutations in the FBN1 gene, which encodes fibrillin-1. MFS is traditionally considered to result from the structural weakness of connective tissue. However, recent investigations on molecular mechanisms indicate that increased transforming growth factor-β (TGF-β) activity plays a crucial role in the pathogenesis of MFS and related disorders, such as Loeys-Dietz syndrome (LDS), which is caused by mutation in TGF-β signaling-related genes. In addition, recent studies show that angiotensin II type 1 receptor (AT1R) signaling enhances cardiovascular pathologies in MFS, and the angiotensin II receptor blocker losartan has the potential to inhibit aortic aneurysm formation. However, the relationship between TGF-β and AT1R signaling pathways remains poorly characterized. In this review, we discuss the recent studies on the molecular mechanisms underlying cardiovascular manifestations of MFS and LDS and the ensuing strategies for management. (Int Heart J 2016; 57: 271-277)

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Characterization of the inflammatory cells in ascending thoracic aortic aneurysms in patients with Marfan syndrome, familial thoracic aortic aneurysms, and sporadic aneurysms

Abstract: These results indicate that the infiltration of inflammatory cells contributes to the pathogenesis of thoracic aortic aneurysms. Superantigen-driven stimulation of T lymphocytes in the aortic tissues of patients with thoracic aortic aneurysms may contribute to the initial immune response.

Cited by 130 publications

References 27 publications

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Genetic contribution in sporadic thoracic aortic aneurysm? Emerging evidence of genetic variants related to TLR-4-mediated signaling pathway as risk determinants

Fibrillin-containing microfibrils are key signal relay stations for cell function

Pathophysiology and Management of Cardiovascular Manifestations in Marfan and Loeys–Dietz Syndromes

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