Key result
Hydrogen sulfide administration significantly attenuated high-salt-induced myocardial fibrosis, fibroblast activation, and collagen synthesis by downregulating hypoxia-inducible factor-1α.
Why the study?
The contribution of the H2S/CBS pathway to high-salt-induced myocardial fibrosis, focusing on the mechanistic involvement of HIF-1α, was not defined.
Does hydrogen sulfide alleviate high-salt-induced myocardial fibrosis in rat models?
Does hydrogen sulfide alleviate high-salt-induced myocardial fibrosis in rat models?
p-value: p=<0.05
Hydrogen sulfide attenuates high-salt-induced myocardial fibrosis by suppressing fibroblast activation and collagen synthesis via downregulation of HIF-1α.
May support H2S/CBS targeting in salt-induced fibrosis; leaves open translation from in vitro data to clinical practice.
Background Endogenous hydrogen sulfide (H 2 S) and its key generating enzyme, cystathionine β-synthase (CBS), prevent vascular remodeling and damage to target organs during the advancement of hypertension induced by a high-salt diet. Objective The contribution of the H 2 S/CBS pathway to high-salt–induced myocardial fibrosis (MF) was explored, with a focus on the mechanistic involvement of hypoxia-inducible factor-1α (HIF-1α). Methods We used primary rat cardiac fibroblasts stimulated with high-salt medium and an MF model induced by a high-salt diet in Dahl salt-sensitive rats. Sodium hydrosulfide (NaHS), a commonly used H 2 S donor, was administered in vitro at 100 μmol/L and in vivo at 90 μmol/kg to maintain adequate H 2 S levels. An HIF-1α stabilizer, dimethyloxalylglycine (DMOG), was used to maintain the HIF-1α protein level. The H 2 S/CBS pathway was followed using Western blotting and a sulfide-sensitive probe. The extent of MF was examined using histological and immunofluorescence staining techniques, including Sirius red and Masson trichrome. We performed Western blot analysis to measure fibrosis-related protein and HIF-1α protein levels. Results High-salt exposure reduced H 2 S production and downregulated CBS protein expression in cardiac fibroblasts both in vitro and in vivo . In vitro , the H 2 S donor inhibited the activation of cardiac fibroblasts triggered by high-salt conditions, while in vivo , it alleviated MF in salt-sensitive rats. From a mechanistic standpoint, high-salt exposure markedly upregulated HIF-1α expression. However, this increase was reversed by pretreatment with H 2 S. Furthermore, the HIF-1α stabilizer DMOG blocked the H 2 S-induced reduction in HIF-1α protein levels and consequently abolished the antifibrotic effect of H 2 S on cardiac fibroblasts exposed to high-salt conditions. Conclusion In conclusion, H 2 S attenuates high-salt-induced MF by suppressing fibroblast activity and collagen synthesis, potentially via downregulation of HIF-1α.
No takes yet. Share an insight, caveat, or question.
Peng et al. (2025) studied Myocardial fibrosis (n=30). Sodium hydrosulfide (NaHS) vs. High-salt diet/medium alone was evaluated on Myocardial fibrosis extent (collagen accumulation and fibroblast activation) (p=<0.05). Hydrogen sulfide administration significantly attenuated high-salt-induced myocardial fibrosis, fibroblast activation, and collagen synthesis by downregulating hypoxia-inducible factor-1α.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: