Matricellular proteins, Thrombospondin-2 en SPARC (Osteonectine) protect against heart failure.

Heart failure affects over 11 million people in the USA and Europe, and is a major cause of hospitalization and mortality. The major causes of heart failure are ischemic heart disease, hypertension and viral infection in the heart. Despite clinical standards, better understenading the pathogenesis of heart failure is essential to improve diagnosis and treatment strategies. Recent findings have shown that 'Matricellular proteins', a group of non-structural glycoproteins present in the extracellular matrix of the heart, possess a crucial, protective and potential therapeutic role when it comes to the integrity and function of the stressed heart. Following upon our exciting preliminary data and by the use of a multidisciplinary research approach, including mouse models and phenotypical analysis, molecular biology and preclinical studies, this project will unravel the biological functions, protective role and clinical potential of Thrombospondin-2 and SPARC, two matricellular proteins, during (i) aging-related cardiomyopathy, (ii) the pathogenesis of heart failure during myocarditis, myocardial infarction and/or hypertension and (iii) the functionality of the heart. Next, I will investigate whether Thrombospondin-2 and/or SPARC could serve as (non-invasive) biomarkers for patients prone to heart failure. Finally, using phenotype-genotype-associations, possible gene mutations and/or polymorphisms in the Thrombospondin-2 and SPARC-gene will be explored as novel cause for dilated cardiomyopathy.

Keywords:Extracellular matrix, Genetics, Remodeling, Matricellular proteins, Heart failure, Cardiovascular system

Disciplines:Cardiac and vascular medicine