Exploring the Correlation Between NLRP3 Activation and Endothelial-to-Mesenchymal Transition in the Heart of a Murine Model of Systemic Sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease marked by fibrosis in various organs, including the heart. Cardiac involvement influences prognosis, but the underpinning mechanisms remain unclear. This study investigates myocardial changes in a murine SSc model induced by subcutaneous injection of HOCl, with a specific focus on alterations in structural proteins and inflammatory markers, oxidative stress, and vascular remodeling. Hearts were collected from SSc mice after 6 weeks, and structural, inflammatory, and oxidative stress markers were evaluated by Hematoxylin and Eosin (H&E) staining, Masson's Trichrome, and immunohistochemical analysis. Increased vimentin and α-SMA expression were detected in the vasculature, indicating endothelial dysfunction and myofibroblast activation, alongside a decrease in CD31 expression, consistent with an endothelial-to-mesenchymal transition (EndMT). Concomitant increases in macrophage (CD68, F4/80, EP29, EPR1) and inflammasome markers (Caspase-1, IL-1β and NLPR-3) were observed together with a remarkably augmented level of MMP3, MMP9, Collagen I and TGF-β, thus suggesting that inflammation and matrix remodeling correlate with endothelial dysfunction. Accordingly, the increased levels of NRF2 and HOMX1 suggested a compensatory protective response against oxidative stress. These data suggest that both immune cell- and inflammasome-mediated inflammation signaling play a key role in endothelial dysfunction by altering the balance between fibrosis and vascular remodeling markers.