Periodic Reporting for period 2 - INTRICARE (International Network for Training on Risks of vascular Intimal Calcification And roads to Regression of cardiovascular diseasE)
Periodo di rendicontazione: 2019-03-01 al 2021-08-31
The objective of INTRICARE is to train a new generation of scientist that will be excellently skilled to expedite our understanding of vulnerable plaque formation, with a particular focus on microcalcification, and to develop innovative solutions for the early prevention, treatment and diagnosis of atherosclerosis.
Phosphorylcholine (PC) and malonedialdehyde (MDA) were identified as antigens and measures levels of natural antibodies IgM antiPC/antiMDA and IgG antiPC/antiMDA in different cohorts of atherosclerosis. This work has been extended to patients suffering from severe and mild COVID symptoms. A novel pathway on the regulation of SMC calcification was discovered, and the Wnt-PPARg signaling was confirmed as crucial in this pathway. The impact of microcalcification on SMC switching towards an osteochondrogenic VSMC phenotype has been investigated using novels models for biochemical initiation of atherogenesis and seven iPSC lines have been registered. Next to iPSC derived iSMCs, primary SMC isolates from different patients have been screened as SMC donors for the use of metabolomics screening. Within the INTRICARE consortium, novel regulatory mechanisms of atherosclerotic microcalcification favouring inflammation have been unravelled. This is also including marker identification and imaging. Fractions from bovine adrenal glands were fractionated and revealed novel mediators of calcification. Co-culturing naïve and activated macrophages and contractile and synthetic SMCs was successfully performed. Next, in vitro data are compared with in vivo imaging of novel cellular regulators of plaque vulnerability established. A first manuscript (accepted) on the correlation of CT with carotid plaque transcriptomes and association of calcification to lesion-stabilisation. PET motion correction using MR data, BOOST sequence for carotid arteries and performance and evaluation of a new dedicated carotid PET/MR coil compared to the Siemens and body coils is done.
INTRICARE research activities gave rise to results that can generate IP, mainly patents, and which have a significant potential for commercial exploitation. We envisage that our research will lead to IP on novel drugs targeting vulnerable plaque formation. Moreover, novel imaging tools/compounds will be developed. As the consortium actively trained its ESRs on valorisation and encouraged the creation of a spin-off company to exploit INTRICARE’s results, ESR13 has founded the company InflaNova in Stockholm that exploits vaccination against phosphatidylcholine to prevent atherosclerosis (https://www.linkedin.com/in/shailesh-kumar-samal).
In sum, INTRICARE research and efforts have led to 59 papers of which were published in open access journals or made open access by the beneficiary including one paper published in the top tier journal “Nature”.