Identification and characterization of small molecule modulators of cardiac hypertrophy

Thesis event information

Date and time of the thesis defence

Place of the thesis defence

Remote access: https://oulu.zoom.us/j/405815167

Topic of the dissertation

Identification and characterization of small molecule modulators of cardiac hypertrophy

Doctoral candidate

Master of Science Marja Tölli

Faculty and unit

University of Oulu Graduate School, Faculty of Medicine, Research Unit of Biomedicine

Subject of study

Pharmacology and Toxicology

Opponent

Professor Ullamari Pesonen, University of Turku

Custos

Professor Jukka Hakkola, University of Oulu

Add event to calendar

Small molecule modulation of cardiac hypertrophy associated with heart failure

This study identified small molecule compounds that are able to modulate cardiac hypertrophy by affecting the function of the key regulatory proteins in heart failure. The aim of the study was to develop methods for the identification of such compounds and the determination of their properties. In various cell culture and animal models, several compounds were found to have an effect on the development of cardiac hypertrophy.

In addition, this study investigated the biosafety of porous silicon micro- and nanoparticles when used for administration of small molecule compounds to cardiac tissue. Micro- and nanosized particles are promising in a variety of medical diagnostic and therapeutic applications.

Heart failure is a clinical syndrome where the heart is unable to pump a sufficient amount of blood into the circulation in response to systemic demand. Typical symptoms are breathlessness, ankle swelling and fatigue. Various pathophysiological stimuli (e.g., pressure overload and myocardial damage) activate several mechanisms (e.g., neurohumoral activation, inflammation, cell death) that lead to myocardial growth and remodeling, and when prolonged, to cardiac dysfunction.

Although the prognosis of patients with heart failure has improved and the number of hospitalization has decreased due to medication, cardiovascular disease remains the leading cause of death worldwide. Therefore, new approaches are needed to enhance the pharmacotherapy of heart failure.

The results of this study suggest that modulation of the key transcription factors involved in cardiac hypertrophy may provide possibilities for novel therapeutic interventions for heart failure. In addition, it was found that porous silicon micro and nanoparticles were applicable as drug delivery carriers into the heart tissue.
Last updated: 15.4.2020