ArticleInternational journal of molecular sciences2021
In Vitro and In Vivo Effects of SerpinA1 on the Modulation of Transthyretin Proteolysis.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 16 citations in OpenAlex.
- Bioinformatics-based study on the regulatory network of lipid metabolism-related genes and mechanisms in coronary heart disease.Hereditas · 2025Article
- Associations between pathophysiological traits and symptom development in retrospective analysis of V30M and V122I transthyretin amyloidosis.International journal of cardiology. Heart & vasculature · 2025Article
- Cardiac Amyloidosis: State-of-the-Art Review in Molecular Pathology.Current issues in molecular biology · 2024Review
- Proteomic Evidence for Amyloidogenic Cross-Seeding in Fibrinaloid Microclots.International journal of molecular sciences · 2024Article
- Neural Correlates and Molecular Mechanisms of Memory and Learning.International journal of molecular sciences · 2024Article
- Emerging Translational Research in Neurological and Psychiatric Diseases: From In Vitro to In Vivo Models.International journal of molecular sciences · 2023Article
- Lessons from the first-in-human in vivo CRISPR/Cas9 editing of the TTR gene by NTLA-2001 trial in patients with transthyretin amyloidosis with cardiomyopathy.Global cardiology science & practice · 2023Article
- Hereditary Transthyretin-Related Amyloidosis: Genetic Heterogeneity and Early Personalized Gene Therapy.Biomedicines · 2022Review
- Neurogenic Inflammation: The Participant in Migraine and Recent Advancements in Translational Research.Biomedicines · 2021Review
- Molecular Mechanisms of Cardiac Amyloidosis.International journal of molecular sciences · 2021Review
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Transthyretin (TTR) proteolysis has been recognized as a complementary mechanism contributing to transthyretin-related amyloidosis (ATTR amyloidosis). Accordingly, amyloid deposits can be composed mainly of full-length TTR or contain a mixture of both cleaved and full-length TTR, particularly in the heart. The fragmentation pattern at Lys48 suggests the involvement of a serine protease, such as plasmin. The most common TTR variant, TTR V30M, is susceptible to plasmin-mediated proteolysis, and the presence of TTR fragments facilitates TTR amyloidogenesis. Recent studies revealed that the serine protease inhibitor, SerpinA1, was differentially expressed in hepatocyte-like cells (HLCs) from ATTR patients. In this work, we evaluated the effects of SerpinA1 on in vitro and in vivo modulation of TTR V30M proteolysis, aggregation, and deposition. We found that plasmin-mediated TTR proteolysis and aggregation are partially inhibited by SerpinA1. Furthermore, in vivo downregulation of SerpinA1 increased TTR levels in mice plasma and deposition in the cardiac tissue of older animals. The presence of TTR fragments was observed in the heart of young and old mice but not in other tissues following SerpinA1 knockdown. Increased proteolytic activity, particularly plasmin activity, was detected in mice plasmas. Overall, our results indicate that SerpinA1 modulates TTR proteolysis and aggregation in vitro and in vivo.
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