Molecular remodeling in atrial fibrillation: protective roles of small HSPs
PhD ceremony: Mr. L. Ke, 12.45 uur, Aula Academiegebouw, Broerstraat 5, Groningen
Dissertation: Molecular remodeling in atrial fibrillation: protective roles of small HSPs
Promotor(s): prof. H.H. Kampinga, prof. R.H. Henning
Faculty: Medical Sciences
Atrial Fibrillation (AF), the most common sustained arrhythmia, is associated with substantial cardiovascular morbidity and mortality. AF has the tendency to become more persistent over time. Recently, an increased awareness of the role of “atrial remodeling” has advanced our understanding of the persistency of AF. The concept “atrial remodeling” defines any changes in atrial function or structure that promote the development of atrial arrhythmia. It can be divided into two principal forms: electrical remodeling and structural remodeling. Both have their specific molecular basis and are also termed as molecular remodeling. With the onset of tachycardia, the rapid and irregular atrial firing substantially causes abnormal electrophysiological properties like Ca2+ overload and subsequent reduction of Ca2+ transients (electrical remodeling). If this progresses, myolysis will occur that hallmarks the initiation of structural remodeling. Myolysis is characterized by degradation of the myofibril structure and leads to contractile dysfunction. In this thesis, we first provide evidence for a major role of calpain in the degradation of troponins (a major group of myofibril proteins) and contractile dysfunction. Using a HL-1 cell model and a newly developed in vivo Drosophila model for AF, we next show that a general upregulation of so-called Heat Shock Proteins (HSP) can effectively inhibit AF-related remodeling. We identified HSPB1, a prominent member of the family of human small HSP, as required and sufficient for this protection and also find other family members (HSPB6, 7, 8) to display similar protective roles. T his thesis therefore provides strong basis for targeting these HSPBs in human AF.
Last modified: | 13 March 2020 12.59 a.m. |
More news
-
29 November 2023
UMCG opent nieuwe faciliteit voor microbioomonderzoek 
Vandaag opent het UMCG de Groningen Microbioom Hub: een nieuwe faciliteit met state-of-the-art technologie waarin alle UMCG-expertise op het gebied van microbioomonderzoek samenkomt. Dit zorgt voor unieke mogelijkheden in onderzoek en maakt nieuwe...
-
28 November 2023
Science: more exciting than showbiz
Science often seems very complicated. Most people probably don't really know what researchers do, and what it takes to make a breakthrough. That is why it is important to keep the general public informed of what is happening in science, says Iris...
-
13 November 2023
UMCG beantwoordt vragen patiënten met hulp van AI
Het UMCG zet kunstmatige intelligentie (artificial intelligence, afgekort AI) in om zorgverleners te helpen bij het beantwoorden van schriftelijke vragen van patiënten. Dit gebeurt in samenwerking met andere ziekenhuizen vanuit de EPIC Nederlandse...