Heart failure, the common clinical syndrome characteristic of advanced cardiac disease of diverse etiologies, is a major cause of morbidity and mortality. Indeed, the incidence and prevalence of heart failure in affluent societies are increasing due to demographics with rising proportion of elderly, as well as increased survival of myocardial infarction. Despite implementation of several new treatment modalities during the last 20 years, heart failure is still a progressive and ominous disease indicating that important pathogenic mechanisms remain unmodified by the most current treatment modalities. Thus, there is an impetus for new and more effective pharmacological interventions.
In evolving heart failure multiple compensatory actions are triggered in order to maintain cardiac output, among which is activation of the sympathetic nervous system, the renin-angiotensin system, as well as a number of autocrine/ paracrine factors synthesized in myocardial tissue. These compensatory actions also reflect in alterations of cardiac structure, collectively called cardiac remodeling. The most important structural changes are cardiac myocyte hypertrophy and myocardial fibrosis. Although cardiac remodeling may initially balance loss of contractile force, the continuum of these structural alterations often feeds into vicious circles leading to progression of cardiac dysfunction. Despite substantial new insights into the mechanisms of myocardial hypertrophy and fibrosis, many of the nodal points that orchestrate these structural alterations still remain to be identified. Thus, an important focus of our research group is to unravel the signal transduction mechanisms that constitute the dysfunctional signaling responses leading to pathologic remodeling of the heart. Another important conceptual approach is that of delineating mechanisms that either increases or decreases the tolerance of cardiac myocytes to hypoxia or free oxygen radical injury, i.e. potential mediators of cardiac myocyte damage in evolving heart failure. The purpose of these investigations is to provide new knowledge of disease mechanisms enabling development of novel pharmacological interventions for heart failure.
Our research group is a multidisciplinary team of experts in gene technology, molecular and cellular biology, as well as experimental and clinical medicine. The research efforts comprise studies of isolated cardiac myocytes and fibroblasts, integrated physiology in genetically engineered mice, large animal studies, as well as clinical investigations. Our research group is member of Center for Heart Failure Research, University of Oslo (www.heartfailure.no), a thematic research initiative and focus area of research selected by the Faculty of Medicine. Center for Heart Failure Research is also a regional research network sponsored by Helse Sør-Øst Regional Health Authority. The Institute for Surgical Research provides infrastructure with state-of-the-art equipment for high-resolution echocardiography and integrated physiologic assessment of cardiac function in both small and large animals.
Dysfunctional cardiac signaling mechanisms and signals astray are considered major causes of pathologic myocardial hypertrophy and predisposition to heart failure. Increasingly, dysfunctional signaling mechanisms are implicated in increased production of free oxygen radicals, mitochondrial dysfunction and reduced tolerance to hypoxia and/or free oxygen radicals per se. Thus, the major goal of our research group is to dissect the function of myocardial autocrine/paracrine factors, their cognate receptors, and intracellular pathways in cardiac myocytes and fibroblasts. New knowledge on the function and mechanisms of signaling pathways in the heart may provide basis for development of new and more effective therapeutic intervention in acute coronary syndromes and heart failure.
Read the annual report 2012 for more information on the activities of the research group
Focus on recruitment and career building in health research
May 24, 2013
May 6, 2013
CCN2/CTGF attenuates myocardial hypertrophy and cardiac dysfunction upon chronic pressure-overload
Int J Cardiol (in press)