Quantitative Proteomics of Plasma-Derived Extracellular Vesicles Reveals a Plasminogen-Centered Protein Network in Transthyretin Cardiac Amyloidosis.

@article{zaroui2026quantitative,
  title = {{Quantitative Proteomics of Plasma-Derived Extracellular Vesicles Reveals a Plasminogen-Centered Protein Network in Transthyretin Cardiac Amyloidosis.}},
  author = {Amira Zaroui and Damien Habert and Benoit Vallée and Mounira Kharoubi and Soraya Fellahi and Benoit Vingert and Michel Seve and Ilaria Cascone and Vincent Audard and Emmanuel Itti and Hajer Abroud and Arnault Galat and Thibaud Damy and Sandrine Bourgoin-Voillard and Valérie Molinier-Frenkel},
  journal = {JACC. Advances},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jacadv.2026.103302},
  url = {https://europepmc.org/article/MED/42854597},
  note = {CC BY},
}

TY  - JOUR
TI  - Quantitative Proteomics of Plasma-Derived Extracellular Vesicles Reveals a Plasminogen-Centered Protein Network in Transthyretin Cardiac Amyloidosis.
AU  - Amira Zaroui
AU  - Damien Habert
AU  - Benoit Vallée
AU  - Mounira Kharoubi
AU  - Soraya Fellahi
AU  - Benoit Vingert
AU  - Michel Seve
AU  - Ilaria Cascone
AU  - Vincent Audard
AU  - Emmanuel Itti
AU  - Hajer Abroud
AU  - Arnault Galat
AU  - Thibaud Damy
AU  - Sandrine Bourgoin-Voillard
AU  - Valérie Molinier-Frenkel
PY  - 2026
DA  - 2026/10/08
JO  - JACC. Advances
DO  - 10.1016/j.jacadv.2026.103302
UR  - https://europepmc.org/article/MED/42854597
AB  - Background  The prognosis of patients with transthyretin cardiac amyloidosis (ATTR) remains poor; this is primarily due to late diagnosis, when irreversible damage has already occurred. Circulating levels of transthyretin or other plasma markers have little value for diagnosis. Although extracellular vesicles (EVs) (key mediators of intercellular communication) may reflect disease-specific molecular changes, their protein cargo has not yet been explored in the context of ATTR cardiomyopathy (ATTR-CM).Objectives  We evaluated whether cardiac amyloidosis alters the proteome of circulating EVs and assessed whether these changes define signature of ATTR.Methods  Plasma EVs were prospectively isolated by ultracentrifugation from 41 patients with confirmed ATTR-CM (ATTR+ group; wild-type ATTR and variant ATTR) and 24 frequency-matched patients with nonamyloid cardiomyopathy (ATTR- group), all referred to the Referral Center for Cardiac Amyloidosis (Henri Mondor Hospital, Créteil, France). EVs were characterized by flow cytometry and analyzed by quantitative liquid chromatography mass spectrometry/mass spectrometry proteomics.Results  ATTR+ patients had a distinct signature enriched in proteins associated with vascular homeostasis, coagulation, and inflammation. At least 18 of these proteins formed an interconnected network centered on plasmin/plasminogen. Notably, EV levels of transthyretin and plasminogen were elevated, whereas the level of alpha2-antiplasmin (plasmin's primary inhibitor) was low. This imbalance is particularly relevant because plasmin is known to promote amyloidogenesis via transthyretin cleavage.Conclusions  These exploratory findings highlight a plasmin/plasminogen-centered protein network linking fibrinolysis, complement activation, and vascular inflammation to ATTR pathophysiology, and suggest that plasma EV proteomics warrant further evaluation as a minimally invasive approach for disease monitoring and biomarker discovery in ATTR-CM.
SN  - 2772-963X
ER  -