Networking & Grants  »  Grants  »  International
XploreCAD

ERA-NET on Cardiovascular Diseases - “Advanced ex vivo analyses and multi-frequency ultrasound technology for improved evaluation and diagnosis of coronary plaque”(ERA-CVD Contract 41/2018) - 2018-2021

Romanian coordinator: Dr. Antohe Felicia

Research Partners:

  • Stiftelsen SINTEF (Consortium coordinator) – Dr. Rune Hansen

  • Institute of Cellular Biology and Pathology N.Simionescu (ICBP) – Dr. Felicia Antohe

  • VERMON SA – Dr. Mathieu Legros

  • Karolinska University Hospital (KUH) - Dr. Kenneth Caidahl

Project acronym: XploreCAD

Duration of the project: 36 months

Atherosclerosis is considered a multifactorial disease, with risk factors ranging from high fat diet, hypertension, smoking, diabetes, to genetic susceptibility and other factors. The general consensus is that myocardial infarction, a hallmark of coronary artery disease (CAD), can be prevented if these known risk factors are taken care of in due time. Classic statin treatment has led to a significant reduction of clinical events, but a considerable residual risk of cardiovascular-related mortality still remains. Alarmins are host biomolecules that can initiate and perpetuate a noninfectious inflammatory response. Myocardial ischemia, the result of coronary artery occlusion, initiates systemic inflammation through the release of such alarmins. Our hypothesis is that alarmins are critical players of CAD plaque progression, which can be directly used for targeted imaging. The XploreCAD project will identify potential markers of CAD that will be used with a novel multi-frequency technology for molecular imaging with intravascular ultrasound, to bring new insights into plaque development and mechanisms related to plaque instability. The methodology will include high performance nano-liquid chromatography mass spectrometric analysis and immunological assays of plaques and sera isolated from atherosclerotic animals and patients. Expected results will lead to a better understanding of the mechanisms of plaque progression and an improved imaging technique for coronary plaque diagnosis and personalized therapy.

 

 

 

 

Figure 1.Illustration of the activities within the XploreCAD project.

 

ERA-NET on Cardiovascular Diseases - “Advanced ex vivo analyses and multi-frequency ultrasound technology for improved evaluation anddiagnosis of coronary plaque(ERA-CVD Contract 41/2018) - 2018-2021

Coordonator roman: Dr. Antohe Felicia

Parteneri implicați:

  • Stiftelsen SINTEF (coordonare) – Dr. Rune Hansen

  • Institute of Cellular Biology and Pathology N.Simionescu (ICBP) – Dr. Felicia Antohe

  • VERMON SA – Dr. Mathieu Legros

  • Karolinska University Hospital (KUH) - Dr. Kenneth Caidahl

 

Acronim:XploreCAD

Durata: 36 luni

Prezentare: Proiectul XploreCAD va identifica markerii potențiali ai CAD care vor fi utilizați cu o nouă tehnologie de tip multi-frecvență pentru imagistica moleculară cu ultrasunete intravasculară, pentru a aduce noi perspective asupra dezvoltării plăcii și a mecanismelor legate de instabilitatea plăcii. Plăcile și serurile de la pacienți și de la iepurii aterosclerotici, cu metabolism lipoproteic similar cu cel oamen, vor fi analizați și comparați prin metode ex vivo avansate. Noul transductor multi-frecvență care urmează să fie dezvoltat va fi adecvat pentru imagistica intravasculară cu ultrasunete (IVUS) a arterei coronare la om. Cu toate acestea, în proiectul curent se va realiza doar o probă preclinică a acestui concept, folosind acest nou traductor intravascular la iepurii aterosclerotici.

Obiectivele principale ale proiectului sunt:

- Studierea expresiei alarminelor (calitativ și cantitativ) în diferite etape ale dezvoltării plăcii aterosclerotice, de la leziunile timpurii până la cele vulnerabile, prin analiza proteomică realizata cu ajutorul spectrometriei de masă de înaltă performanță, pentru a identifica biomarkeri cu potențial predictiv în stratificarea riscului la pacienții CAD.

- Proiectarea și producerea unui traductor intravascular de multi-frecvență, care va fi testat și validat într-un model de iepure aterosclerotic utilizând noi secvențe de imagistică cu frecvență multiplă, atât cu microbule simple, cât și cu cele țintite.

Pentru atingerea acestor obiective vor fi realizate:

  • Studii experimentale prin care se va analiza expresia proteică a alarminelor în diferite stadii ale evoluției plăcii aterosclerotice în iepurii hipercolesterolemici NZW (New Zealand White) vs. control.

  • Studii clinice dedicate evaluării alarminelor selectate în plăcile umane și în probele serice recoltate de la pacienții aterosclerotici, pentru potențialul lor de afi utilizati ca biomarkeri ai stadiului de dezvoltare a plăcii aterosclerotice (de la apariția acesteia și până la rupere). Ne vom concentra pe alarminele diferențiat exprimate în plăcile și serurile prelevate de la animalele luate în studiu.

 


 

STAGE I:

 

Preliminary studies to evaluate the hypercholesteraemic diet and the treatment to be used in rabbit atherosclerotic model.

 

 (zoom in by clicking the image)

 

Hyperlipidemic diet induces atherosclerotic plaque progression

 

 

Atherosclerotic lesions assessed by hematoxylin and eosin staining. A: high fat diet; B: anti-hyperlipidemia treatment; C: control.

 (zoom in by clicking the image)

 

Preliminary results:

- The hypercholesterolemic diet induces atherosclerotic plaque progression in rabbit model.

- The 0.5% cholesterol diet will be extended to 12 weeks.

- The anti PCSK9 antibody demonstrated to be effective in decreasing the LDL plasma concentration.

 

 (zoom in by clicking the image)

 

Hyperlipidaemia induced significant increase in lipid plasma parameters.

 

 

http://www.clinicaladvisor.com

 (zoom in by clicking the image)

 

 

 

The new experimental protocol proposed for the next stage

 

 

(zoom in by clicking the image)

 


 

Results dissemination Stage I 2018

 

-   OMICS frontiers for personalized medicine. Antohe Felicia.12thCentral and Eastern European Proteomics Conference (CEEPC) and ICBP NS scientific sesion, 24-26 October, 2018, Bucharest, Romania. ISBN 978-606-023-012-0. (Book of  Abstracts, page 21; please click on the book image)

 

 

- Biomarker search in chronic non-communicable diseases using mass spectrometry based proteomics. Felicia Antohe.12thCentral and Eastern European Proteomics Conference (CEEPC) and ICBP NS scientific sesion, 24-26 October, 2018, Bucharest, Romania. ISBN 978-606-023-012-0.

 

-    Proteomic alterations induced by poly (2-ethyl butyl cyanoacrylate) nanoparticles. V.I. Suica, E. Uyy, L. Ivan, R.M. Boteanu, R. Hansen, Y. Mørch, F. Antohe.12thCentral and Eastern European Proteomics Conference (CEEPC) and ICBP NS scientific sesion, 24-26 October, 2018, Bucharest, Romania. ISBN 978-606-023-012-0. (Book of  Abstracts, page 46; please click on the book image)

 

 

-   Exploration of mechanism leading to plaque instability in a rabbit atherosclerotic model. Preliminary data. Luminita Ivan, Elena Uyy, Raluca Maria Boteanu, Viorel Iulian Suica, Cristin Coman, Sigrid Berg, Rune Hansen, Felicia Antohe. 12th Central and Eastern European Proteomics Conference (CEEPC) and IBPC NS scientific sesion, 24-26 October 2018, Bucharest, Romania. ISBN 978-606-023-012-0. 

 

-   Mass Spectrometry evidence for modified protein composition of pulmonary lipid rafts in experimental diabetes. E. Uyy, V.I. Şuică, R.M. Boteanu, L. Ivan, F. Antohe, M. Simionescu. The 12th Central and Eastern European Proteomic Conference (CEEPC) jointly with The 39th Anniversary of the Institute of Cellular Biology and Pathology “Nicolae Simionescu”, October 24 – 26, 2018, Bucharest, Romania. ISBN 978-606-023-012-0. 

 


 

Stage II 

PROGRESS REPORT – 2nd year