Chronic inflammation: A key role in degeneration of bicuspid aortic valve

Manno, Girolamo; Bentivegna, Riccardo; Morreale, P; Nobile, Domenico; Santangelo, A.; Novo, Salvatore; Novo, Giuseppina

doi:10.1016/j.yjmcc.2019.03.013

Cited by 19 publications

(16 citation statements)

References 76 publications

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“…Inflammation may have the most crucial role in BAV degeneration. Inflammatory process maintained by the presence of increased shear stress includes various mechanisms such as the collection of inflammatory cells and release of cytokines, oxidative stress, and endothelial dysfunction [15]. Various mechanisms, in different forms of the BAV, may be heterogeneously responsible.…”

Section: Discussionmentioning

confidence: 99%

Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

Karaduman¹,

Ayhan²,

Keleş³

et al. 2020

Turk J Med Sci

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Background/aim: From a pathophysiological point of view, inflammation is thought to be more dominant in bicuspid aortic valve (BAV) stenosis than tricuspid aortic valve (TAV) stenosis. Our study aimed to determine the association between monocyte to highdensity lipoprotein cholesterol (HDL-C) ratio (MHR), a new inflammatory marker, and the speed of progression of stenosis and pathophysiology of BAV stenosis. Materials and methods: A total of 210 severe aortic stenosis patients (70 consecutive BAV patients, 140 matched TAV patients) were retrospectively enrolled in the study. Clinical and echocardiographic data and laboratory results related to our research were collected retrospectively from the patients' records. MHR was measured as the ratio of the absolute monocyte count to the HDL-C value. Results: Seventy BAV (mean age: 72.0 ± 9.1 years, 42.9% female) and 140 TAV patients (mean age: 77.9 ± 8.3 years, 51.4% female) with severe aortic stenosis were enrolled in this study. There was no difference between the two groups in terms of another baseline demographic or clinic findings except age (P < 0.001). Monocyte count, hemoglobin level, mean platelet volume was significantly higher, and HDL-C level was significantly lower in the BAV group, while other lipid and CBC parameters were found to be similar. In the multivariate analysis, MHR (P = 0.005, 95% CI: 0.90-0.98) and, as expected, age (P = 0.001, 95% CI: 1.02-1.11) were found to be significant as the independent predictor of BAV, after adjusting for other risk factors. Conclusion: Our study showed a significant correlation between increased MHR and BAV. MHR was determined as a significant independent predictor for the speed of progression and diagnosis of severe BAV stenosis in multivariate analysis.

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Section: Discussionmentioning

confidence: 99%

Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

Karaduman¹,

Ayhan²,

Keleş³

et al. 2020

Turk J Med Sci

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“…Importantly, the mechanisms of progressive AS differ based on their subtypes. In Type I - fusion of the right and left coronary cusps - oxidative stress predominates, while in Type II - fusion of the right and non-coronary cusps - endothelial dysfunction is the main contributor 69 . These however converge on the common pathway of inflammation, leading to subsequent valvular tissue remodelling and fibro-calcification.…”

Section: Oxidative Stress In Bicuspid Aortic Valvesmentioning

confidence: 99%

The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications

Phua¹,

Chew²,

Kong³

et al. 2022

Theranostics

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Despite the elucidation of the pathways behind the development of aortic stenosis (AS), there remains no effective medical treatment to slow or reverse its progress. Instead, the gold standard of care in severe or symptomatic AS is replacement of the aortic valve. Oxidative stress is implicated, both directly as well as indirectly, in lipid infiltration, inflammation and fibro-calcification, all of which are key processes underlying the pathophysiology of degenerative AS. This culminates in the breakdown of the extracellular matrix, differentiation of the valvular interstitial cells into an osteogenic phenotype, and finally, calcium deposition as well as thickening of the aortic valve. Oxidative stress is thus a promising and potential therapeutic target for the treatment of AS. Several studies focusing on the mitigation of oxidative stress in the context of AS have shown some success in animal and in vitro models, however similar benefits have yet to be seen in clinical trials. Statin therapy, once thought to be the key to the treatment of AS, has yielded disappointing results, however newer lipid lowering therapies may hold some promise. Other potential therapies, such as manipulation of microRNAs, blockade of the renin-angiotensin-aldosterone system and the use of dipeptidylpeptidase-4 inhibitors will also be reviewed.

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“…However, because of high risks of the surgery for the elderly patients and postoperative complications with anticoagulant medicines, the surgical treatment is not suitable for all CAVD patients. Previously considered as a passive consequence of aging ( 7 ), CAVD is now recognized as an active disease driven by chronic inflammation ( 120 ). Molecular signaling pathways underlying inflammation are thus potential targets for the disease diagnosis and intervention.…”

Section: Notch Signaling In Aortic Valve Homeostasis and Calcificationmentioning

confidence: 99%

NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease

Wang

Fang

et al. 2021

Front. Cardiovasc. Med.

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NOTCH intercellular signaling mediates the communications between adjacent cells involved in multiple biological processes essential for tissue morphogenesis and homeostasis. The NOTCH1 mutations are the first identified human genetic variants that cause congenital bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). Genetic variants affecting other genes in the NOTCH signaling pathway may also contribute to the development of BAV and the pathogenesis of CAVD. While CAVD occurs commonly in the elderly population with tri-leaflet aortic valve, patients with BAV have a high risk of developing CAVD at a young age. This observation indicates an important role of NOTCH signaling in the postnatal homeostasis of the aortic valve, in addition to its prenatal functions during aortic valve development. Over the last decade, animal studies, especially with the mouse models, have revealed detailed information in the developmental etiology of congenital aortic valve defects. In this review, we will discuss the molecular and cellular aspects of aortic valve development and examine the embryonic pathogenesis of BAV. We will focus our discussions on the NOTCH signaling during the endocardial-to-mesenchymal transformation (EMT) and the post-EMT remodeling of the aortic valve. We will further examine the involvement of the NOTCH mutations in the postnatal development of CAVD. We will emphasize the deleterious impact of the embryonic valve defects on the homeostatic mechanisms of the adult aortic valve for the purpose of identifying the potential therapeutic targets for disease intervention.

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Chronic inflammation: A key role in degeneration of bicuspid aortic valve

Cited by 19 publications

References 76 publications

Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

Association between monocyte to high-density lipoprotein cholesterol ratio and bicuspid aortic valve degeneration

The mechanistic pathways of oxidative stress in aortic stenosis and clinical implications

NOTCH Signaling in Aortic Valve Development and Calcific Aortic Valve Disease

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