title: The role of titin and extracellular matrix remodelling in heart failure with preserved ejection fraction.
abstract: Heart failure with preserved ejection fraction (HFpEF) is characterised by a high incidence of metabolic comorbidities that share the potential to induce both systemic and coronary microvascular inflammation and oxidative stress. These pathophysiological alterations contribute to increased passive stiffness of the myocardium and to diastolic dysfunction, both hallmarks of HFpEF. Passive myocardial stiffness depends mainly on two components: the extracellular matrix (ECM) and the cardiomyocytes. Quantitative and qualitative changes in collagen metabolism leading to myocardial fibrosis determine the ECM-based stiffness of the myocardium. Different noninvasive diagnostic tools to assess myocardial fibrosis are being developed, some of which have demonstrated to correlate with clinical status and prognosis. Cardiomyocytes mainly alter the passive stiffness through alterations in the giant myofilament titin, which serves as a spring. By modifying its phosphorylation state or by direct oxidative effects, titin determines cardiomyocyte-based passive stiffness. Probably the relative importance of cardiomyocyte-based changes is more important in the beginning of the disease, whereas ECM-based changes become more prominent in the more advanced stages. The present review focuses on these changes in ECM and cardiomyocytes in HFpEF and their potential prognostic and therapeutic implications.
authors.affiliation: ICaR-VU, VU University Medical Center, Van der Boechorststraat 7, 1081, BT Amsterdam, The Netherlands. c.franssen@vumc.nl.
authors.forename: C
authors.initials: C
authors.lastname: Franssen
authors.affiliation: Center for Applied Medical Research, University of Navarra, Program of Cardiovascular Diseases, Pamplona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: González Miqueo
keywords: Biomarkers; Extracellular matrix; HFpEF; Myocardial remodelling; Myocardial stiffness; Titin