Additionally, celastrol, a natural compound and nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) inhibitor, can mitigate aortic valve fibrosis by upregulating GSK-3β gene expression in cultured porcine aortic valvular interstitial cells (AVICs) and the rabbit calcific aortic valve disease (CAVD) models, as evidenced by attenuated fibrotic marker FN 80. This evidence concerns the gene CYBB and congenital bilateral aplasia of vas deferens from CFTR mutation.