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Progetto vincitore della Borsa di Studio SISA 2016 - Morieri

 

 

PPAR-alpha Variants as Modulators of Fenofibrate Cardiovascular Effectiveness in patients with type 2 diabetes

Mario Luca Morieri

 


Abstract:


Background: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in type 2 diabetes (T2D). Fenofibrate, a PPAR-alpha agonist known to improve diabetic dyslipidemia, has been proposed as a drug to prevent CVD in diabetic patients. However, results of clinical trials have been mixed. My hypothesis is that these disappointing results hide a genetic heterogeneity in the CVD response to fenofibrate.
Objective: In collaboration with Dr. Alessandro Doria (Joslin Diabetes Center/Harvard Medical School), I have identified two single nucleotide polymorphisms (SNPs) in the gene coding for PPAR-alpha - the target of fenofibrate - showing dramatic effects on the ability of this drug to reduce CVD events in the ACCORD-Lipid trial. The objective of this proposal is to dissect the pathways through which these SNPs exert such modulatory effect.

Methods and Research strategy: I intend to pursue this goal through two complementary approaches:
1. At the clinical level I will assess whether the influence of the PPAR-alpha SNPs on fenofibrate CVD effectiveness is mediated by an effect on lipid metabolism and/or inflammation. This will be accomplished by evaluating the association between these two SNPs and lipid and inflammatory biomarkers in ACCORD-Lipid.
2. At the molecular level I will analyze the effect of the two SNPs, and their interaction with fenofibrate, on the expression of PPAR-alpha and its downstream target genes through in vitro experiments in two human cell types relevant to atherogenesis.

Expected results: If successful, this project will provide further confirmation of the modulatory role of these genetic variants, allowing us to build genetic prediction models to select T2D patients who are most likely to
benefit from fenofibrate,thereby rescuing a cardio-protective therapy that would be otherwise dismissed as
ineffective. By dissecting the pathways involved in this genetic effect, this research may also point to other
key pharmacological targets to prevent CVD in T2D.


 

 

 

Presentazione del progetto vincitore di Borsa di Studio SISA - 2016

 

 

 


Area Soci

Eventi

33° Congresso Nazionale


33° Congresso Nazionale

Roma, 24-26 novembre 2019
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Congresso Regionale SISA Sezione Toscana

Pisa, 7-8 Giugno 2019

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Congresso Regionale SISA Sezione Lazio

Roma, 8 Giugno 2019

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Congresso Regionale SISA Sezione Triveneto

Padova, 11 Maggio 2019

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Congresso congiunto SIIA umbro-marchigiana SISA Umbria 2019

Narni (TR), 2 Marzo 2019

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Spring Meeting Gruppi Giovani SIIA, SIMI, SISA 2019

Rimini,
28 febbraio - 2 marzo 2019

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EAS Advanced Course in Rare Lipid Disease

Cinisello B.mo (Mi), 19 Ottobre 2018

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Giornale Italiano Arteriosclerosi

Rivista in lingua italiana
riservata ai Soci S.I.S.A.
Ultimo numero:
Anno 9 • N.4/2018

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Rivista NMCD

Nutrition, Metabolism and Cardiovascular Diseases

Istruzioni per l'accesso online

IF 2017: 3.318


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EAS Advanced Course in Rare Lipid Disease
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Progetto vincitore della Borsa di Studio "Andrea Mezzetti" 2017
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