Network-Guided Multiomic Mapping of Aortic Valve Calcification

Blaser, Mark C.; Kraler, Simon; Lüscher, Thomas F.; Aikawa, Elena

doi:10.1161/atvbaha.122.318334

Cited by 6 publications

(2 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Network-based integration methods are applied in the analysis of CAVD-derived multi-omics and have become an important tool for better understanding the molecular regulatory networks of CAVD initiation, pathogenesis, and treatment 53 , 54 . By analyzing the gene regulatory networks via RNA-seq, NOTCH1 haploinsufficiency was identified as a potential risk factor for BAV and CAVD 55 .…”

Section: Discussionmentioning

confidence: 99%

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation

Chen,

Ren,

Xie

et al. 2024

Nat Commun

View full text Add to dashboard Cite

Calcific aortic valve disease is a prevalent cardiovascular disease with no available drugs capable of effectively preventing its progression. Hence, an efficient drug delivery system could serve as a valuable tool in drug screening and potentially enhance therapeutic efficacy. However, due to the rapid blood flow rate associated with aortic valve stenosis and the lack of specific markers, achieving targeted drug delivery for calcific aortic valve disease has proved to be challenging. Here we find that protease-activated-receptor 2 (PAR2) expression is up-regulated on the plasma membrane of osteogenically differentiated valvular interstitial cells. Accordingly, we develop a magnetic nanocarrier functionalized with PAR2-targeting hexapeptide for dual-active targeting drug delivery. We show that the nanocarriers effectively deliver XCT790—an anti-calcification drug—to the calcified aortic valve under extra magnetic field navigation. We demonstrate that the nano-cargoes consequently inhibit the osteogenic differentiation of valvular interstitial cells, and alleviate aortic valve calcification and stenosis in a high-fat diet-fed low-density lipoprotein receptor-deficient (Ldlr−/−) mouse model. This work combining PAR2- and magnetic-targeting presents an effective targeted drug delivery system for treating calcific aortic valve disease in a murine model, promising future clinical translation.

show abstract

Section: Discussionmentioning

confidence: 99%

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation

Chen,

Ren,

Xie

et al. 2024

Nat Commun

View full text Add to dashboard Cite

show abstract

“…Immune cell patterns revealed an increase in M0 macrophages and memory B cells as potential therapeutic targets. Research on rats has linked vascular calcification to chaperone genes and ER stress due to nicotine and vitamin D. Another study involving transcatheter aortic valve implantation (TAVI) in severe AS patients emphasized the role of microparticles in vascular health assessment 30 – 38 .…”

Section: Molecular Mechanisms Of Developmentmentioning

confidence: 99%

Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies

Jain,

Goyal,

Khan

et al. 2024

Annals of Medicine &Amp; Surgery

View full text Add to dashboard Cite

Aortic valve stenosis is a disease characterized by thickening and narrowing of the aortic valve (AV), most commonly due to calcification, which leads to left ventricular outflow obstruction called calcific aortic valve disease (CAVD). CAVD presents as a progressive clinical syndrome with cardiorespiratory symptoms, often with rapid deterioration. The modern-day pathophysiology of CAVD involves a complex interplay of genetic factors, chronic inflammation, lipid deposition, and valve calcification, with early CAVD stages resembling atherosclerosis. Various imaging modalities have been used to evaluate CAVD, with a recent trend of using advanced imaging to measure numerous AV parameters, such as peak jet velocity. Significant improvements in mortality have been achieved with transcatheter AV repair, but numerous therapeutics and modalities are being researched to delay the progression of CAVD. This article aims to provide a comprehensive review of CAVD, explore recent developments, and provide insights into future treatments with various novel modalities.

show abstract

Immunotherapy in the Context of Aortic Valve Diseases

Bartoli-Leonard,

Pennel,

Caputo

2024

Cardiovasc Drugs Ther

View full text Add to dashboard Cite

Purpose Aortic valve disease (AVD) affects millions of people around the world, with no pharmacological intervention available. Widely considered a multi-faceted disease comprising both regurgitative pathogenesis, in which retrograde blood flows back through to the left ventricle, and aortic valve stenosis, which is characterized by the thickening, fibrosis, and subsequent mineralization of the aortic valve leaflets, limiting the anterograde flow through the valve, surgical intervention is still the main treatment, which incurs considerable risk to the patient. Results Though originally thought of as a passive degeneration of the valve or a congenital malformation that has occurred before birth, the paradigm of AVD is shifting, and research into the inflammatory drivers of valve disease as a potential mechanism to modulate the pathobiology of this life-limiting pathology is taking center stage. Following limited success in mainstay therapeutics such as statins and mineralisation inhibitors, immunomodulatory strategies are being developed. Immune cell therapy has begun to be adopted in the cancer field, in which T cells (chimeric antigen receptor (CAR) T cells) are isolated from the patient, programmed to attack the cancer, and then re-administered to the patient. Within cardiac research, a novel T cell–based therapeutic approach has been developed to target lipid nanoparticles responsible for increasing cardiac fibrosis in a failing heart. With clonally expanded T-cell populations recently identified within the diseased valve, their unique epitope presentation may serve to identify novel targets for the treatment of valve disease. Conclusion Taken together, targeted T-cell therapy may hold promise as a therapeutic platform to target a multitude of diseases with an autoimmune aspect, and this review aims to frame this in the context of cardiovascular disease, delineating what is currently known in the field, both clinically and translationally.

show abstract

Network-Guided Multiomic Mapping of Aortic Valve Calcification

Cited by 6 publications

References 56 publications

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation

Enhancing aortic valve drug delivery with PAR2-targeting magnetic nano-cargoes for calcification alleviation

Insights into calcific aortic valve stenosis: a comprehensive overview of the disease and advancing treatment strategies

Immunotherapy in the Context of Aortic Valve Diseases

Contact Info

Product

Resources

About