Personal information of the project director:

Name:  SILAGHI Cristina Alina Md. Ph

Project : Postdoctoral research project

Code  : 682

Lenght of project : 24 months  (2010-2012)

Budget : 337777 lei

 

 

Title: STUDY OF PRO-INFLAMMATORY ADIPOKINES AND OF THE METABOLISM OF CORTISOL IN THE EPICARDIAL ADIPOSE TISSUE AND THE RELATIONSHIP WITH THE CORONARY ARTERY DISEASE

 

 

Project Summary

EPICARDIAL ADIPOSE TISSUE (EAT) REPRESENTS A SOURCE OF PRO-INFLAMMATORY FACTORS DIRECTLY INVOLVED IN CORONARY ATHEROGENESIS. ADIPOKINES AND LOCALLY PRODUCED HORMONES COULD PASS THROUGH THE ARTERIAL WALL DUE TO DIRECT CONTACT BETWEEN MYOCARDIUM, VESSELS AND FAT WITHOUT INTERPOSITION OF A FASCIA. THIS OUTSIDE TO INSIDE FENOMENON WAS DEMONSTRATED AND EXPLAINS THE IMPORTANCE OF LOCAL FACTORS IN ATHEROGENESIS. RECENT WORKS SHOW THAT ULTRASOUND MEASUREMENT OF EAT REPRESENTS AN IMPORTANT PARAMETER FOR THE VISCERAL ADIPOSITY, CORRELATED WITH THE METABOLIC SYNDROME. THE PROJECT CONSISTS IN ACHIEVING EAT AND SUBCUTANEOUS ADIPOSE TISSUE (SAT) BIOPSIES IN PATIENTS WITH AND WITHOUT CORONARY DISEASE AND ASSESSMENT OF INFLAMMATORY ADIPOKINE EXPRESSION OR CERTAIN ELEMENTS OF THE EXTRACELULAR MATRIX BY PROTEIN-CHAIN-REACTION ANALYSIS. THE AIM IS TO ASSESS THE IMPLICATIONS OF EAT IN THE CORONARY ATHEROSCLEROSIS IN SIGHT OF NEW ANTI-ATHEROSCLEROTIC THERAPIES AVAILABLE IN THE NEAR FUTURE.

THE PROJECT PROPOSES:

- ULTRASOUND MEASUREMENT OF EAT AND CORRELATIONS WITH CARDIOVASCULAR RISK FACTORS AND VISCERAL ADIPOSE TISSUE MEASURED BY COMPUTED TOMOGRAPHY

- MORPHOLOGICAL EVALUATION OF EAT (ADIPOCITE MEASUREMENTS, VASCULARIZATION AND MACROPHAGICAL INFILTRATION) IN PATIENTS WITH AND WITHOUT CORONARY DISEASE, COMPARATIVE FOR EAT AND SAT

- STUDY OF LOCAL METABOLISM OF CORTISOL (11BETA HYDROXYSTEROID DEHYDROGENASE, GLUCOCORTICOID RECEPTORS) AND 2 INFLAMMATORY ADIPOKINES (PAI-1 AND CATHEPSINE S) INVOLVED IN ATHEROGENESIS IN EAT IN PATIENTS WITH AND WITHOUT CORONARY DISEASE, COMPARATIVE BETWEEN EAT AND SAT

- STUDY OF HYPOXIA INDUCIBLE FACTOR (HIF-1) IN EAT IN PATIENTS WITH CORONARY DISEASE AND ASSESSMENT OF NEW CORRELATIONS WITH MACROPHAGICAL INFILTRATION, PAI-1, CATHEPSIN S AND CORTISOL METABOLISM

- STUDY OF METALLOPROTEASIS INHIBITOR-1 AS PARAMETER OF EXTRACELLULAR MATRIX AND CORRELATIONS WITH HIF-1 AND CORONARY STATUS

- IDENTIFICATION OF NEW GENES INVOLVED IN ATHEROGENESIS BY DNA MICROARRAYS

 

The objectives that we propose in the present study are: 

- Ultrasound evaluation of EAT and assessment of correlations with the clinical and biological parameters (smoking, circumference of waist, dyslipidemia, insulin-resistance) of the metabolic syndrome and of the cardiovascular risk and with VAT measured by CT.

- Morphological characterization of the epicardial adipose tissue (measurement of adipocytes sizes, evaluation of the degree of tisular vascularization, severity of macrophagic infiltration) and comparison of these parameters to the parameters found in SAT in patients with and without coronary disease. We will analyze if the EAT morphology is similar to the morphology of visceral AT, as known in specialty literature.

- Study by PCR of the expression of a protein of hemostasis (PAI-1), of an adipokine with implications in atherogenesis (CTSS), of a marker of local hypoxia (HIF-1) and the local metabolism of cortisol (11beta hidroxisteroid dehydrogenase, receptors of glucocorticoids, promoters of receptors of glucocorticoids) in EAT that have not been studied so far in this tissue. The comparison of results between the coronary and non-coronary patients to highlight the importance of coronary status for their genic expression. We will follow the link that exists between HIF-1 and the other adipokines, respectively how the hypoxia influences the genic expression of other parameters in EAT. 

- Study of metalloproteases inhibitor 1 as parameter of extracellular matrix and evaluation of connection with hypoxia and coronary status.  

- Study of transcriptome by technique of DNA bio-chips and identification of target genes, paths of regulation or metabolic paths characteristic for EAT.

 

Total budget for 2010: 97330 lei

Budget structure for 2010:

Staff expenses: 30000 lei

Indirect costs: 5630 lei

Logistics costs: 53700 lei

Mobility expenses: 8000lei

 

Objectives for 2010:

Elaboration of study protocol and formation of material basis

Definition of inclusion and exclusion criteria and elaboration of patient informed consent files. Selection of patients

Logistics: laptop, PC, fax, printer; consumables

Materials necessary for biological samples, biopsy of adipose tissue  Necessary kits for the extraction of  RNA, PCR technique

Formation of witness group and of coronary disease patients group 

Application of questionnaires for patients evaluation 

Biochemical analysis, biopsies and their storage

CT Imaging

 

 

 

 

Results for 2010:

 

It was elaborated and accepted for publication the following article:

Is Epicardial Adipose Tissue Assessed by Echocardiography a Reliable Method for Visceral Adipose Tissue Prediction?

Alina Silaghi, Laura Poanta, Raluca Pais, Horatiu Silaghi

Medical Ultrasonography

 

It was elaborated for publication the following articles (actually in course of evaluation):

Glucocorticoid metabolism in human epicardial adipose tissue:role of coronary status

Alina Silaghi, Raluca Pais, Traian Scridon, Horatiu Silaghi, Vincent Achard

 

Human epicardial adipose tissue: the relationship with coronary artery disease.

Alina Silaghi, Raluca Pais, Ana Valea, Aurel I. Mironiuc, Horatiu Silaghi

 

 

Contact

Silaghi Cristina Alina: mail adress alinasilaghi@yahoo.com