ArticleJournal of translational medicine2023
Pharmacological inhibition of the cysteine protease cathepsin C improves graft function after heart transplantation in rats.
Article in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Cardiac remodelling and dysfunction in cancer patients receiving cardiotoxic therapies: proteomic and metabolomic profiling.European heart journal · 2026Article
- It's a Trap!-Potential of Cathepsins in NET Formation.International journal of molecular sciences · 2025Review
- Protective effects of neutrophil serine protease inhibition against ischemia-reperfusion injury in lung or heart transplantation.The FEBS journal · 2025Review
- Exosomes derived from microRNA-540-3p overexpressing mesenchymal stem cells promote immune toleranceWorld journal of stem cells · 2024Article
- Genetics of Cardiac Aging Implicate Organ-Specific Variation.medRxiv : the preprint server for health sciences · 2024Article
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10 authors.
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Abstract
backgroundHeart transplantation (HTX) is the standard treatment for end-stage heart failure. However, reperfusion following an ischemic period can contribute to myocardial injury. Neutrophil infiltration, along with the subsequent release of tissue-degrading neutrophil elastase (NE)-related serine proteases and oxygen-derived radicals, is associated with adverse graft outcomes. The inhibition of cathepsin C (CatC) has been shown to block NE-related protease activation. We hypothesized that the CatC inhibitor BI-9740 improves graft function after HTX.
methodsIn a rat model of HTX, the recipient Lewis rats were orally administered with either a placebo (n = 12) or BI-9740 (n = 11, 20 mg/kg) once daily for 12 days. Donor hearts from untreated Lewis rats were explanted, preserved in a cardioplegic solution, and subsequently heterotopically implanted. In vivo left-ventricular (LV) graft function was assessed after 1 h of reperfusion. The proteolytic activity of neutrophil serine proteases was determined in bone marrow lysates from BI-9740-treated and control rats. Additionally, myocardial morphological changes were examined, and heart samples underwent immunohistochemistry and western blot analysis.
resultsThe NE-related proteolytic activity in bone marrow cell lysates was markedly decreased in the BI-9740-treated rats compared to those of the placebo group. Histopathological lesions, elevated CatC and myeloperoxidase-positive cell infiltration, and nitrotyrosine immunoreactivity with an increased number of poly(ADP-ribose) polymerase (PARP)-1-positive cells were lowered in the hearts of animals treated with BI-9740 compared to placebo groups. Regarding the functional parameters of the implanted graft, improvements were observed in both systolic function (LV systolic pressure 110 ± 6 vs 74 ± 6 mmHg; dP/dt
conclusionsWe provided experimental evidence that pharmacological inhibition of CatC improves graft function following HTX in rats.
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