Novel molecular factors in cardiac hypertrophic response
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Auditorium of Pharmacology F202 (Aapistie 5B)
Topic of the dissertation
Novel molecular factors in cardiac hypertrophic response
Doctoral candidate
Licentiate of Medicine Hanna Säkkinen
Faculty and unit
University of Oulu Graduate School, Faculty of Medicine, Department of Biomedicine, Pharmacology and Toxicology
Subject of study
Biomedicine
Opponent
Professor Eero Mervaala, University of Helsinki
Custos
Professor Jaana Rysä, University of Eastern Finland
Novel molecular factors in cardiac hypertrophic response
The molecular mechanisms responsible for left ventricular (LV) remodeling and heart failure (HF) have been extensively studied, and this research has been instrumental in developing pharmacological treatments decreasing mortality in HF patients. However, there is no cure for HF if heart transplantation is not an option.
Transcriptomics studies have provided a tool for screening activated genes in diseased tissue. The goal of my research was to characterize the role of four selected genes from microarray screenings in cardiac hypertrophic response. Tumour necrosis factor -like weak inducer of apoptosis (TWEAK), fibroblast growth factor inducible 14 (Fn14), regenerating islet-derived 3 gamma (Reg3γ), and dyxin, known as LIM and cysteine-rich domains 1, have been previously shown to be upregulated in different experimental models of cardiac stress.
The expression and regulation of TWEAK, Fn14 and Reg3γ were examined in different models of cardiac stress in vivo and in vitro. In addition, the effect of intramyocardial adenoviral gene transfer-inducing overexpression of dyxin on cardiac structure and function was examined during angiotensin II (Ang II)-induced hypertension. The study showed that Fn14 and Reg3γ were rapidly upregulated due to pressure overload and post-infarction remodeling in vivo along with some known inducers of cardiac myocyte hypertrophy in vitro. Immunohistochemical analysis showed that Reg3γ was mainly localized in myofibroblasts in the inflammatory area, while Fn14 showed progressive immunoreactivity in fibroblasts. TWEAK was localized in cardiac myocytes and endothelial cells, but it did not respond to any of the hypertrophic stimuli. Overexpression of cardiac dyxin resulted in thickening of LV structure during Ang II-induced hypertension together with attenuation of the activation of certain cardiac hypertrophy-associated genes.
My research provides new information on the gene expression of novel factors in pathological cardiac hypertrophy as well as new insights for pharmacological therapies in HF.
Transcriptomics studies have provided a tool for screening activated genes in diseased tissue. The goal of my research was to characterize the role of four selected genes from microarray screenings in cardiac hypertrophic response. Tumour necrosis factor -like weak inducer of apoptosis (TWEAK), fibroblast growth factor inducible 14 (Fn14), regenerating islet-derived 3 gamma (Reg3γ), and dyxin, known as LIM and cysteine-rich domains 1, have been previously shown to be upregulated in different experimental models of cardiac stress.
The expression and regulation of TWEAK, Fn14 and Reg3γ were examined in different models of cardiac stress in vivo and in vitro. In addition, the effect of intramyocardial adenoviral gene transfer-inducing overexpression of dyxin on cardiac structure and function was examined during angiotensin II (Ang II)-induced hypertension. The study showed that Fn14 and Reg3γ were rapidly upregulated due to pressure overload and post-infarction remodeling in vivo along with some known inducers of cardiac myocyte hypertrophy in vitro. Immunohistochemical analysis showed that Reg3γ was mainly localized in myofibroblasts in the inflammatory area, while Fn14 showed progressive immunoreactivity in fibroblasts. TWEAK was localized in cardiac myocytes and endothelial cells, but it did not respond to any of the hypertrophic stimuli. Overexpression of cardiac dyxin resulted in thickening of LV structure during Ang II-induced hypertension together with attenuation of the activation of certain cardiac hypertrophy-associated genes.
My research provides new information on the gene expression of novel factors in pathological cardiac hypertrophy as well as new insights for pharmacological therapies in HF.
Last updated: 23.1.2024