About Cardiology

The Laboratory for Experimental Cardiology at Maastricht University, part of the Department of Cardiology at Maastricht UMC+ (MUMC+), conducts Cardiovascular research and teaches classes at the Medical School, University College and the Science College.

Research at the Laboratory for Experimental Cardiology is embedded in the “Cardiac hypertrophy and heart failure” cluster in the School for Cardiovascular Diseases (CARIM), where multiple principal investigators, each with a group of postdocs, PhD students and technicians do their science. The research in the fields of Inflammation, Extracellular Matrix, Gene Regulation and Electricity and Arrhythmogenesis of the heart is of high international standard and covers a broad range of fundamental mechanistic studies and aims to be translational towards clinical care.

Research Cardiology

Matricellular proteins and heart failure.

Two important systems in the matrix are the structural proteins like collagens, and the non-structural proteins, the matricellular proteins. Increased expression of matrix metalloproteinases (MMPs) during HF causes degradation of collagen fibers,  myocyte slippage and increased inflammation, whereas enhanced expression of matricellular proteins are protective, by promoting myocyte survival, decreasing inflammation, and stimulating the production of a qualitative matrix. These matricellular proteins are a group of non-structural glycoproteins present in the interstitial matrix, including thrombospondins, mimecan, stabilin-1 and SPARC (osteonectin), among others. They do not play a direct structural role in the heart, but regulate interactions between the matrix and cardiomyocytes, fibroblasts and inflammatory cells.  Their expression is low in the normal heart, but reappears at high levels during cardiac injury or stress, such as hypertension and ischemia. The research program obtained strong evidence that matricellular proteins protect against the adverse inflammatory response during hypertensive and ischemic heart disease. This is substantiated by the more pronounced inflammatory, hypertrophic and fibrotic response in the hearts of mice lacking the matrix proteins thrombospondin-2, mimecan, stabilin-1 or osteonectin (SPARC). These findings indicate that inflammatory cells interact with cardiomyocytes and fibroblasts, and that matrix proteins produced by these inflammatory cells regulate the crosstalk towards hypertrophic and pro-fibrotic signaling pathways.
Therefore, the primary aims of this program are to unravel the implication of the matricellular proteins at the level of each individual cardiac cell:  inflammatory cells, fibroblasts, cardiomyocytes and endothelial cells. The molecular mechanisms by which these matricellular proteins alter cardiomyocyte survival/hypertrophy, promote matrix maturation, and prevent adverse inflammation will be addressed. We aim to find out which are the molecular partners on cell membrane regulating their protective effect on cardiomyocyte survival, the downstream  signalling cascade and the resulting changes in hypertrophy, inflammatory and fibrotic targets. 

Inflammation-mediated microRNA’s and cardiac disease.

Last 3 years, our laboratory opened a completely new area of research, investigating the yet unknown role for inflammation-related non-coding RNAs in heart failure in general, and viral myocarditis in particular.  A major microarray analysis of microRNA’s at different time points of viral myocarditis, pressure overload and dilated cardiomyopathy was performed both in mice and humans, unravelling major inflammation microRNA signals, and identifying novel microRNA targets implicated in cardiac inflammation and HF.
The overall objective of this research line is to unravel the precise biological role of specific inflammation-mediated microRNA’s (microRNA’s)and their regulation in cardiac injury and dysfunction following viral infection, and in hypertrophy and fibrosis during hypertensive heart disease . Whereas recent studies mainly focused on the role of cardiomyocyte- and fibroblast-derived microRNA’s in hypertrophy, fibrosis and arrhythmias, this program will unravel the biological role of the inflammation-derived microRNA’s in cardiac disease.  By combining microRNA knockout animal experiments, the use of antagomirs, and in vitro studies,  this program is currently addressing the role of particular inflammation-derived microRNA’s in both hypertensive heart disease and viral myocarditis. It is expected that inflammation-mediated microRNA’s play a crucial role in the susceptibility to cardiac injury following viral infection of the heart, and mediate hypertrophy and fibrosis during hypertension