Development of BIOnanotechnologies based on Extracellular Vesicles for early diagnosis, prognosis and therapy of atherosclerotic disease (BIOVEA)
Various biomarkers have been proposed for the diagnosis and prognosis of acute coronary syndrome, however none for stable coronary disease. Identification of biomarkers that augment established clinical indicators, may allow earlier diagnosis of coronary disease, as well as improved recognition of the risk of complications and cardiovascular death. Additionally, this would pave the way for biomarkers, such as extracellular vesicles, to be employed as precise therapeutic agents in these diseases.
Role of Caveolin-1 in age-associated vascular amyloidosis (CANVAS)
Project funded by the Ministry of Education and Research, PN-10N/2023-23.16.01.01
Coordinator: Victor Babeș National Institute of Pathology (IVB), Prof Dr. Mihail Eugen Hinescu & Conf. Dr. Mihaela Gherghiceanu
Core team: Daciana Marta, Ana Maria Enciu, Elena Codrici, Tudor Emanuel Fertig, Maria Dobre, Iuliana Ciocănea-Teodorescu, Maria Dudău, Victor-Eduard Peteu, George Terinte-Balcan
Age-associated amyloidosis results from abnormal, multi-organ accumulation of fibrils, formed by a variety of precursor proteins, some still uncharacterized. With the exception of transthyretin-derived senile systemic amyloidosis, there are currently no available diagnostic tests and no targeted therapies for this family of diseases.
CANVAS is a preclinical, proof-of-concept study, which aims to characterize the specific role of caveolin-1 (Cav1) in the pathogenesis of age-associated vascular amyloidosis, using a wide range of complementary approaches from the fields of genomics, proteomics and structural biology.
(1) Development of an experimental 3D vascular model/organoid allowing an in-depth study of the molecular mechanisms leading to amyloidogenesis in the context of Cav1 deficiency;
(2) Study of molecular mechanisms leading to amyloidogenesis in a Cav1-deficient mouse model;
(3) Investigation of potential associations between amyloidosis and Cav1 deficiency in human patients;
(4) Development of an in vitro CRISPR/Cas9 system to block amyloidogenesis by reintroducing deficient gene(s), with potential future therapeutic applications.
We expect to successfully generate an in vitro experimental model which allows studying pathways leading to amyloid deposition in Cav1 deficiency and subsequently, development of biomarkers for the early diagnosis of this potential disease subtype. We also expect to confirm the association between amyloid formation and Cav1-deficiency in a mouse model and human patients and to characterize amyloid deposition in various tissues, including heart and kidney, using advanced bioimaging techniques.
Amyloid deposition in kidney (left: optical microscopy, right: electron microscopy)