Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease

Porras, Ana Maria; Westlund, Jennifer A; Evans, Austin D; Masters, Kristyn S.

doi:10.1073/pnas.1704637115

Cited by 36 publications

(29 citation statements)

References 77 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1H and 1I, for macrophages, ND: 3.38%±1.19%, HFD: 7.65%±2.52%, P<0.05), indicating the valves suffered from inflammation. Previous literatures also supported activation of myofibroblastic VICs, CD4 + T cells and macrophages in inflammatory aortic valve [19,20] .…”

Section: Up-regulation Of Il17a-il17ra Axis In Aortic Valve Of Hfd Apsupporting

confidence: 55%

Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

et al. 2020

View full text Add to dashboard Cite

Interleukin 17A (IL17A) is reported to be involved in many inflammatory processes, but its role in aortic valve diseases remains unknown. We examined the role of IL17A based on an ApoE-/mouse model with strategies as fed with high-fat diet or treated with IL17A monoclonal antibody (mAb). 12 weeks of high-fat diet feeding can elevate cytokines secretion, inflammatory cells infiltration and myofibroblastic transition of valvular interstitial cells (VICs) in aortic valve. Moreover, diet-induction accelerated interleukin 17 receptor A (IL17RA) activation in VICs. In an IL17A inhibition model, the treatment group was intra-peritoneally injected with anti-IL17A mAb while controls received irrelevant antibody. Functional blockade of IL17A markedly reduced cellular infiltration and transition in aortic valve. To investigate potential mechanisms, NF-κB was co-stained in IL17RA + VICs and IL17RA + macrophages, and further confirmed by Western blotting in VICs. High-fat diet could activate NF-κB nuclear translocation in IL17RA + VICs and IL17RA + macrophages and this process was depressed after IL17A mAb-treatment. In conclusion, highfat diet can lead to IL17A upregulation, VICs myofibroblastic transition and inflammatory cells infiltration in the aortic value of ApoE-/mice. Blocking IL17A with IL17A mAb can alleviate aortic valve inflammatory states.

show abstract

Section: Up-regulation Of Il17a-il17ra Axis In Aortic Valve Of Hfd Apsupporting

confidence: 55%

Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The signaling pathway is confirmed with decreased AoV mineralization when using Ki16425, an inhibitor of LPAR1, in Ldlr −/− , ApoB 100/100 mice fed with high fat and high sucrose diet ( 39 ). It is important to mention that changes in the ECM, with accumulation of glycosaminoglycans, precede and favor oxLDL retention ( 24 , 41, 42 ).…”

Section: Introductionmentioning

confidence: 99%

“…Besides activation of endothelial cells ( 11 , 12 ), OxLDLs trigger proinflammatory cytokines expression and promotes infiltration of immune cells into AoV leaflets ( 42 , 51, 52 ). In diseased AoV, higher oxLDL content correlates with higher amounts of inflammatory cells ( 53 ) .…”

Section: Introductionmentioning

confidence: 99%

“…In response to pathological stimuli, VICs differentiate into osteoblast-like cells with abnormal expression of typical bone genes, including Runx2, Alkaline Phosphatase (ALP), Osteopontin (SPP1) , Osteocalcin ( BGLAP ) ( 47 ) resulting in calcified ECM. Apart from promoting inflammation, OxLDLs and Lp(a) can also directly activate VICs through LPAR1 ( 38 , 39 ) and TLR activation ( 52, 77 – 79 ), This interaction contributes to trigger GAG accumulation, in a positive feedback loop, and upregulates osteogenic gene expression through BMP2 and IL6 expression ( 38 , 42 , 80 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets

Hulin

Hego

Lancellotti

et al. 2018

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Calcific Aortic Valve Disease (CAVD) is the most common heart valve disease and its incidence is expected to rise with aging population. No medical treatment so far has shown slowing progression of CAVD progression. Surgery remains to this day the only way to treat it. Effective drug therapy can only be achieved through a better insight into the pathogenic mechanisms underlying CAVD. The cellular and molecular events leading to leaflets calcification are complex. Upon endothelium cell damage, oxidized LDLs trigger a proinflammatory response disrupting healthy cross-talk between valve endothelial and interstitial cells. Therefore, valve interstitial cells transform into osteoblasts and mineralize the leaflets. Studies have investigated signaling pathways driving and connecting lipid metabolism, inflammation and osteogenesis. This review draws a summary of the recent advances and discusses their exploitation as promising therapeutic targets to treat CAVD and reduce valve replacement.

show abstract

“…Similar results have been reported for human VICs isolated from sclerotic valves ( 146 ). However, several models using native VICs and VECs to produce in vitro TEHV aim to model the pathological development of prosthetic degeneration, calcification and fibrosis by mimicking native-like environments rather than to design prosthetic solutions ( 203 , 204 ). Other studies have used native resident cells to establish tissue engineering and cell culture protocols ( 147 , 176 , 205 ).…”

Section: Scaffolds For In Vitro Tehvmentioning

confidence: 99%

Cell Sources for Tissue Engineering Strategies to Treat Calcific Valve Disease

Jover

Fagnano

Angelini

et al. 2018

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

Cardiovascular calcification is an independent risk factor and an established predictor of adverse cardiovascular events. Despite concomitant factors leading to atherosclerosis and heart valve disease (VHD), the latter has been identified as an independent pathological entity. Calcific aortic valve stenosis is the most common form of VDH resulting of either congenital malformations or senile “degeneration.” About 2% of the population over 65 years is affected by aortic valve stenosis which represents a major cause of morbidity and mortality in the elderly. A multifactorial, complex and active heterotopic bone-like formation process, including extracellular matrix remodeling, osteogenesis and angiogenesis, drives heart valve “degeneration” and calcification, finally causing left ventricle outflow obstruction. Surgical heart valve replacement is the current therapeutic option for those patients diagnosed with severe VHD representing more than 20% of all cardiac surgeries nowadays. Tissue Engineering of Heart Valves (TEHV) is emerging as a valuable alternative for definitive treatment of VHD and promises to overcome either the chronic oral anticoagulation or the time-dependent deterioration and reintervention of current mechanical or biological prosthesis, respectively. Among the plethora of approaches and stablished techniques for TEHV, utilization of different cell sources may confer of additional properties, desirable and not, which need to be considered before moving from the bench to the bedside. This review aims to provide a critical appraisal of current knowledge about calcific VHD and to discuss the pros and cons of the main cell sources tested in studies addressing in vitro TEHV.

show abstract

Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease

Cited by 36 publications

References 77 publications

Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

Advances in Pathophysiology of Calcific Aortic Valve Disease Propose Novel Molecular Therapeutic Targets

Cell Sources for Tissue Engineering Strategies to Treat Calcific Valve Disease

Contact Info

Product

Resources

About