Research projects
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1. AT2 receptor stimulation by aneurysm
Project leader: Elena Kaschina
Abdominal aortic aneurysm (AAA) is a common vascular disorder, which causes significant mortality. We are interested in the role of the renin-angiotensin-aldosterone system (RAAS) in aneurysm formation. In previous studies, we could show an effective reduction of aortic diameter in experimental AAA after treatment with the AT1 receptor (AT1R) antagonist telmisartan. Angiotensin AT2 receptor (AT2R) activation often promotes opposing effects to those of the AT1R such as anti-inflammation, vasodilatation and inhibition of cell proliferation. Therefore, we explored the effects of AT2R activation by AAA. To this purpose, we applied the selective nonpeptide AT2R agonist, Compound 21, for the treatment of experimental AAA.
2. Cannabinoid CB1 and CB2 receptors in vascular remodeling
Project leader: Elena Kaschina
The endocannabinoid system plays a pivotal role in cardiovascular regulation. Both endocannabinoids and their receptors, CB1 and CB2, are present in the heart and vessels. Our previous findings demonstrated the protective role of the CB1 receptor inhibition in the heart. Blocking of this receptor improved cardiac functions in the early and late stages after myocardial infarction. Pharmacological regulation of cannabinoid receptors may also be important for the treatment of vascular diseases. Therefore, in the current project we want to investigate the impact of CB1 and CB2 receptors in prevention of pathological processes in vessels such as proteolysis, cell death, extracellular matrix degradation and remodeling.
3. Selective sodium-glucose cotransporter 2 (SGLT2) inhibition by Empagliflozin in the heart
Project leader: Elena Kaschina
Sodium-glucose cotransporters (SGLTs) mediate cotransport of glucose with sodium in mammalian cells. Recently, SGLT2s have attracted attention for their role in cardiac protection because their inhibition with empagliflozin by patients with diabetes mellitus type 2 reduced hospitalization rates due to heart failure. Thus, SGLT2 inhibitors not only improve the blood glucose level, but also show cardiovascular and renal protective effects irrespective of glucose reduction. Modulation of SGLT2 signalling may offer new perspectives for treatment of coronary heart disease and heart failure. However, the cardioprotective mechanisms of SGLT2 inhibitors are not completely understood because SGLT2 is not expressed in the heart. We aim to explore the cardiac effects of empagliflozin and the underlying mechanisms of its action.