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Myocardial remodeling and reverse remodeling in pressure overload

Our group is conducting experimental/translational research studying cardiac pathophysiology related to aortic stenosis and pressure overload.

About the group

Aortic stenosis is the most common valvular lesion in the western world. In patients with aortic stenosis, excessive myocardial remodeling (hypertrophy, fibrosis and expression of fetal genes) leads to increased operative risk during aortic valve replacement (AVR). There is currently no effective treatment for postoperative low-output syndrome due to diastolic dysfunction, making this a major challenge in cardiac surgery. Incomplete reverse remodeling after AVR for aortic stenosis is associated with persisting symptoms and increased mortality. Hence, studies addressing myocardial remodeling and reverse myocardial remodeling are warranted.

We have established a mouse model of reversible left ventricular pressure overload mimicking AVR for aortic stenosis and found novel extracellular matrix (ECM) changes during reverse remodeling. To extend these findings we have planned further studies including a “loss of function” approach.

We will use a collagen VIII knock out mouse to examine the importance of this collagen isoform in remodeling and reverse remodeling after relief of pressure overload.

Another important aim has been to reveal the importance of the SMAD2 signalling system in pressure overload. We have found that inhibition of SMAD2 by a small peptide inhibitor (SM16) improves cardiac function, possibly due to effects on SERCA2 and intracellular calcium handling.

We are currently also investigating whether specific changes in the extracellular matrix determines whether a pressure overloaded heart is transformed from compensated to decompensated heart failure.

Cooperation

We have a close collaboration with Professors Geir Christensen and Ivar Sjaastad.

 

Published Mar. 28, 2011 3:43 PM - Last modified June 4, 2014 9:02 AM

Contact

Group leader

Participants

Detailed list of participants