Molecular mechanisms of heart diseases

Principal investigator: Professor Heikki Ruskoaho.

Our lab studies the molecular mechanisms of heart failure and myocardial remodeling. Heart failure is one of the most serious challenges for modern cardiovascular medicine. The key pathophysiological process that ultimately leads to heart failure is myocardial remodeling, frequently caused by myocardial infarction or hypertension. Despite optimal treatment with existing drugs, the prognosis of patients with heart failure is poor, and novel therapeutic strategies are necessary to prevent and reverse myocardial remodeling. We have focused to understand the intracellular signaling pathways, transcriptional regulatory factors and epigenetic mechanisms in the adult heart after ischemic injury and in hypertension. We have also explored the role of natriuretic peptides (ANP and BNP) and stretch-activated remodeling mechanisms in response to cardiovascular diseases. Our long-term goal is to understand the complex interactions that modulate myocardial repair and regeneration and to apply this information to novel small molecule therapeutics of myocardial infarction and heart failure

Current research projects include:

Transcription factors in cardiac disease
Transcription factor GATA4, in particular, is a critical regulator of key biological processes in myocardial remodeling and repair. We are continuing to explore the role of GATA4 in heart disease and as a target for therapeutic manipulation.

Novel factors in myocardial remodelling and heart failure
With collaborators, we are investigating the role of novel autocrine/paracrine factors in myocardial remodeling and heart failure and genes identified by genome-wide association studies using in vitro and in vivo models.

MicroRNA regulation of myocardial repair
MicroRNAs are regulated in heart disease and modify levels of cardiac messenger RNAs (mRNAs) regulating their translation. We are studying their role in myocardial remodeling and repair in relevant animals models.

Manipulation of heart repair and regeneration with small molecules
We have designed a discovery platform to identify novel small molecules that might promote cardiac gene expression and are dissecting the mechanisms of action of these cardioprotective molecules.