GATA5 and Endothelial Nitric Oxide Synthase Expression in the Ascending Aorta Is Related to Aortic Size and Valve Morphology

Henn, Dominic; Perttunen, Hilja; Gauer, Simon; Schmied, Wolfram; Porras, Carlos; Such, Miguel; Schäfers, Hans‐Joachim

doi:10.1016/j.athoracsur.2014.02.050

Cited by 13 publications

(15 citation statements)

References 24 publications

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“…78 Furthermore, significantly higher expression of GATA5 and endothelial nitric oxide synthase in the ascending aortas of patients with UAV disease versus BAV and TAV disease has been recently reported. 79 Another recent study 80 demonstrated decreased long-term survival in patients with UAV undergoing isolated AVR when compared with patients with UAV who underwent simultaneous aortic surgery.…”

Section: Patient Phenotypesmentioning

confidence: 99%

The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve–related aortopathy: Full online-only version

Borger

Fedak

Stephens

et al. 2018

The Journal of Thoracic and Cardiovascular Surgery

218

185

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Bicuspid aortic valve disease is the most common congenital cardiac disorder, being present in 1% to 2% of the general population. Associated aortopathy is a common finding in patients with bicuspid aortic valve disease, with thoracic aortic dilation noted in approximately 40% of patients in referral centers. Several previous consensus statements and guidelines have addressed the management of bicuspid aortic valve-associated aortopathy, but none focused entirely on this disease process. The current guidelines cover all major aspects of bicuspid aortic valve aortopathy, including natural history, phenotypic expression, histology and molecular pathomechanisms, imaging, indications for surgery, surveillance, and follow-up, and recommendations for future research. It is intended to provide clinicians with a current and comprehensive review of bicuspid aortic valve aortopathy and to guide the daily management of these complex patients.

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Section: Patient Phenotypesmentioning

confidence: 99%

The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve–related aortopathy: Full online-only version

Borger

Fedak

Stephens

et al. 2018

The Journal of Thoracic and Cardiovascular Surgery

218

185

View full text Add to dashboard Cite

show abstract

“…Spatial analysis by Mohamed and colleagues [23] revealed higher eNOS protein in the concave region of the ascending aorta compared with the convex region within a BAV group, but unlike Aicher and colleagues [22], reported no differences in eNOS between BAV and TAV specimens from corresponding regions [23]. In contrast to findings of decreased eNOS in BAV, eNOS gene expression in specimens from the convexity of the aorta was higher in BAV than in TAV [24]. In our cohort, compared with samples from TAV patients, BAV specimens exhibited increased eNOS gene and protein expression in the R aortic region (the anterolateral segment), which constitutes much of the so-called greater curvature or convexity of the ascending aorta.…”

Section: Commentmentioning

confidence: 99%

“…Lee and colleagues [21] observed the BAV morphology in 5 of 12 eNOS-knockout mice. Others have reported differential eNOS expression in BAV patients through histologic and biologic assessment [22–24]. However, no definitive pattern of eNOS expression has emerged.…”

mentioning

confidence: 99%

Regional Disruptions in Endothelial Nitric Oxide Pathway Associated With Bicuspid Aortic Valve

Kotlarczyk

Billaud

Green

et al. 2016

The Annals of Thoracic Surgery

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Background. Endothelial nitric oxide (NO) synthase (eNOS) has been implicated in the development of bicuspid aortic valve (BAV) and with differential expression in the ascending aorta of BAV patients. However, little is known about functional disruptions in the eNOS pathway and the effect on BAV-associated aortic dilatation. We tested the hypothesis that eNOS function is regionally diminished in ascending thoracic aortic aneurysms associated with BAV. Methods. Thoracic aortic aneurysms specimens were collected from patients with BAV (n [ 21) or tricuspid aortic valve (n [ 12). Tissue samples were harvested from three circumferential regions corresponding to locations above the right, left, and noncoronary sinuses. Adventitial-stripped specimens containing media and intima only were analyzed for NO synthase 3 gene expression and total eNOS protein. Indicators of eNOS activity (pSer1177-eNOS) and NO bioavailability (phosphorylation of vasodilator-stimulated phosphoprotein at Ser239) were also measured. Results. NO synthase 3 and eNOS protein were elevated in the right aortic region of BAV specimens compared with tricuspid aortic valve specimens. Activation of eNOS, as indicated by pSer1177-eNOS, was higher in BAV specimens across all regions. Despite increases in eNOS and pSer1177-eNOS, BAV specimens displayed no change in pSer239-vasodilator-stimulated phosphoprotein compared with tricuspid aortic valve specimens. Conclusions. BAV is associated with regional disruptions in the eNOS pathway, most markedly in the right aortic region. The discrepancy between increased eNOS activity and the absence of increased NO bioavailability in this region provides insight into physiologic mechanisms potentially underlying the asymmetric dilatation pattern observed in BAV.

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“…Notably, circulating PECAM + microparticles were significantly decreased in patients who underwent aortic valve surgery, establishing endothelial damage in BAV individuals probably due to exposure to nonphysiological blood flow, although the possibility of an inherited defect synergizing hemodynamic factors cannot be ruled out. Several laboratories that focused on eNOS content in the AscA reported a differential expression of eNOS between BAV and TAV aneurysmal patients, both at transcriptional and translational levels (85)(86)(87)(88).…”

Section: Endothelial Abnormality In Bav Patientsmentioning

confidence: 99%

Endothelial/Epithelial Mesenchymal Transition in Ascending Aortas of Patients With Bicuspid Aortic Valve

Maleki

Poujade

Bergman

et al. 2019

Front. Cardiovasc. Med.

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Thoracic aortic aneurysm (TAA) is the progressive enlargement of the aorta due to destructive changes in the connective tissue of the aortic wall. Aneurysm development is silent and often first manifested by the drastic events of aortic dissection or rupture. As yet, therapeutic agents that halt or reverse the process of aortic wall deterioration are absent, and the only available therapeutic recommendation is elective prophylactic surgical intervention. Being born with a bicuspid instead of the normal tricuspid aortic valve (TAV) is a major risk factor for developing aneurysm in the ascending aorta later in life. Although the pathophysiology of the increased aneurysm susceptibility is not known, recent studies are suggestive of a transformation of aortic endothelium into a more mesenchymal state i.e., an endothelial-to-mesenchymal transition in these individuals. This process involves the loss of endothelial cell features, resulting in junction instability and enhanced vascular permeability of the ascending aorta that may lay the ground for increased aneurysm susceptibility. This finding differentiates and further emphasizes the specific characteristics of aneurysm development in individuals with a bicuspid aortic valve (BAV). This review discusses the possibility of a developmental fate shared between the aortic endothelium and aortic valves. It further speculates about the impact of aortic endothelium phenotypic shift on aneurysm development in individuals with a BAV and revisits previous studies in the light of the new findings.

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GATA5 and Endothelial Nitric Oxide Synthase Expression in the Ascending Aorta Is Related to Aortic Size and Valve Morphology

Cited by 13 publications

References 24 publications

The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve–related aortopathy: Full online-only version

The American Association for Thoracic Surgery consensus guidelines on bicuspid aortic valve–related aortopathy: Full online-only version

Regional Disruptions in Endothelial Nitric Oxide Pathway Associated With Bicuspid Aortic Valve

Endothelial/Epithelial Mesenchymal Transition in Ascending Aortas of Patients With Bicuspid Aortic Valve

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