Cardiac fibroblasts
MR activation induced an up-regulation in collagen synthesis in rat cardiac fibroblasts (Brilla et al., 1994; Zhou et al., 1996) as well as collagen type I, collagen type III and collagen type VI expressions in adult human cardiac fibroblasts (Martínez-Martínez et al., 2017b). The mechanisms that mediates aldosterone/MR-induced collagen accumulation involved the increase in the pro-inflammatory and pro-fibrotic molecule galectin-3 (Gal-3) (Martínez-Martínez et al., 2015), the induction of tissue inhibitor of metalloproteinases-1 (TIMP-1) expression (Hung et al., 2016), or the augmentation of neutrophil gelatinase-associated lipocalin (NGAL) (Martínez-Martínez et al., 2017a). Moreover, using a quantitative proteomic approach, A kinase anchoring protein (AKAP)-12 was identified as a mediator of aldosterone/MR-induced oxidative stress in human cardiac fibroblasts that leads to mitochondrial dysfunction (Ibarrola et al., 2018). Taken together, these findings support the involvement of cardiac fibroblast-MR pathway activation in fibrosis and oxidative stress.