2022
DOI: 10.1161/circulationaha.121.054108
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Genes That Escape X Chromosome Inactivation Modulate Sex Differences in Valve Myofibroblasts

Abstract: Background: Aortic valve stenosis (AVS) is a sexually dimorphic disease, with women often presenting with sustained fibrosis and men with more extensive calcification. However, the intracellular molecular mechanisms that drive these clinically important sex differences remain under explored. Methods: Hydrogel scaffolds were designed to recapitulate key aspects of the valve tissue microenvironment and serve as a culture platform for sex-specific valvular… Show more

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Cited by 44 publications
(60 citation statements)
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“…Further, the fibronectin-derived peptide sequence (RGD) was conjugated to the material through an azide functionality at 2 mM to promote VIC-matrix interactions. [34][35][36]42 Using this material system, we first sought to determine if VIC mechanosensitivity was consistent with previous observations using materials synthesize from alternative chemistries. 28,35,43 To establish VIC phenotype response to crosslinking density changes in the DBCO-azide PEG hydrogel system, we cultured VICs on both soft and stiffened hydrogels and measured the relative mRNA expression levels of various fibrotic factors (Figure 1C).…”
Section: Stiffness-induced Vic Myofibroblast Activation and Prolifera...mentioning
confidence: 67%
See 3 more Smart Citations
“…Further, the fibronectin-derived peptide sequence (RGD) was conjugated to the material through an azide functionality at 2 mM to promote VIC-matrix interactions. [34][35][36]42 Using this material system, we first sought to determine if VIC mechanosensitivity was consistent with previous observations using materials synthesize from alternative chemistries. 28,35,43 To establish VIC phenotype response to crosslinking density changes in the DBCO-azide PEG hydrogel system, we cultured VICs on both soft and stiffened hydrogels and measured the relative mRNA expression levels of various fibrotic factors (Figure 1C).…”
Section: Stiffness-induced Vic Myofibroblast Activation and Prolifera...mentioning
confidence: 67%
“… 30 In this work, the elastic moduli of the soft and stiff hydrogels ranged from 1.5 kPa initially to 15 kPa after stiffening (Figure 2B). Further, the fibronectin‐derived peptide sequence (RGD) was conjugated to the material through an azide functionality at 2 mM to promote VIC‐matrix interactions 34–36,42 …”
Section: Resultsmentioning
confidence: 99%
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“…Since valve fibrosis is sexually dimorphic, FRET-based calcium sensors may be particularly useful to investigate sex dimorphisms in calcium shuttling in contractile cardiomyocytes and other cardiac cells. 19,20…”
Section: Tags and Reportersmentioning
confidence: 99%