Cardiomyocyte Sprouty1 and Vascular endothelial zinc finger 1 in regulation of cardiac function and disease
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
the University of Oulu Faculty of Medicine, Auditorium F202 (Aapistie 5B)
Topic of the dissertation
Cardiomyocyte Sprouty1 and Vascular endothelial zinc finger 1 in regulation of cardiac function and disease
Doctoral candidate
Master of Science, Pharmacist Tarja Alakoski
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Research Unit of Biomedicine and Internal Medicine
Subject of study
Pharmacology and Toxicology
Opponent
Professor Pasi Tavi, A.I. Virtanen Institute for Molecular Sciences, Faculty of Health Sciences, University of Eastern Finland
Custos
Professor Risto Kerkelä, Research Unit of Biomedicine and Internal Medicine, Faculty of Medicine, University of Oulu
Cardiomyocyte Sprouty1 and Vascular endothelial zinc finger 1 in regulation of cardiac function and disease
Cardiovascular diseases are the most common causes of death in the world. Finding new therapeutic targets is essential to improve the survival and quality of life of patients with cardiovascular diseases. The aim of this thesis was to investigate the role of two proteins, Sprouty1 (Spry1) and Vascular Endothelial Zinc Finger 1 (Vezf1), in the regulation of myocardial cell function and the development of heart disease.
Spry1 has known functions, but its role in the heart is poorly understood. This thesis investigated the role of Spry1 in damage caused by hypoxia and subsequent oxygenation of the heart (ischemia-reperfusion injury) and in pathological left ventricular remodeling. Deletion of Spry1, specifically in cardiomyocytes, reduced troponin I release and reduced cardiac tissue damage after ischemia-reperfusion injury. Long-term deletion of Spry1 in cardiomyocytes led to the development of myocardial fibrosis.
Vezf1 is known to regulate endothelial cell function and vascular development. The results of this thesis show that Vezf1 is present in cardiomyocytes and the expression levels are reduced in diseased hearts. Studies in zebrafish and cardiomyocyte cultures showed that the absence of Vezf1 impairs disease-induced cardiac growth and contractile response. Further studies showed that Vezf1 regulates β-myosin heavy chain (β-MHC).
Together, these findings indicate a role for Spry1 as a modulator of cardiomyocyte survival and fibrotic remodeling, and Vezf1 as a regulator of the cardiac contractile function. These data may be important in the development of targeted therapies to cardiovascular pathologies.
Spry1 has known functions, but its role in the heart is poorly understood. This thesis investigated the role of Spry1 in damage caused by hypoxia and subsequent oxygenation of the heart (ischemia-reperfusion injury) and in pathological left ventricular remodeling. Deletion of Spry1, specifically in cardiomyocytes, reduced troponin I release and reduced cardiac tissue damage after ischemia-reperfusion injury. Long-term deletion of Spry1 in cardiomyocytes led to the development of myocardial fibrosis.
Vezf1 is known to regulate endothelial cell function and vascular development. The results of this thesis show that Vezf1 is present in cardiomyocytes and the expression levels are reduced in diseased hearts. Studies in zebrafish and cardiomyocyte cultures showed that the absence of Vezf1 impairs disease-induced cardiac growth and contractile response. Further studies showed that Vezf1 regulates β-myosin heavy chain (β-MHC).
Together, these findings indicate a role for Spry1 as a modulator of cardiomyocyte survival and fibrotic remodeling, and Vezf1 as a regulator of the cardiac contractile function. These data may be important in the development of targeted therapies to cardiovascular pathologies.
Last updated: 6.10.2025