Cardiac Epigenetics

Research group: Lutz Hein

Cardiac myocytes - The heart is the first organ to develop prenatally. Cardiac myocytes differentiate into cardiac pacemakers, cells of the conduction system and the working myocardium. Cardiac myocytes stop proliferating around birth, but continue to grow by increasing cell size by physiological hypertrophy. Upon injury, e.g. hypertension or myocardial ischemia, surviving cardiac myocytes grow by pathological hypertrophy. This process is facilitated by a pathological gene expression program.

Chronic heart failure - Severe injury of the heart activates neuroendocrine systems (sympathetic and renin-angiotensin systems) which attempt to support the heart in the short term. However, chronically adrenaline/noradrenaline and angiotensin II/aldosterone elicit detrimental effects. They stimulate hypertrophy, inflammation and fibrosis of the heart - a process which is termed 'cardiac remodelling'.

Pharmacotherapy of heart failure - In patients with chronic heart failure with reduced ejection fraction, several drugs can be used to inhibit overactivity of adrenergic and renin-angiotensin-aldosterone systems. Beta blockers, ACE inhibitors, AT1 antagonists, and aldosterone antagonists can reduce morbidity and mortality, but they do not cure the underlying structural heart disease.

Aims - Thus the main research aims are to uncover the epigenetic mechanisms which drive pathological gene expression in heart disease and to pharmacologically modulate cardiac remodelling.

Research methods
- In vitro differentiated cardiac myocytes, model organisms, translational studies
- Sorting of cells or nuclei from cardiac tissue by flow cytometry
- Next generation sequencing (RNA, ChIP, ATAC, DNA methylation)
- Single cell sequencing
- Bioinformatics (www.cardiacepigenome.org)
- Pharmacology: small molecule inhibitors, CRISPR/Cas, gene targeting