Project lead: Jana Grune, Wolfgang M. Kübler

Staff: Lara Läschke, Ceren Kocana

The majority of patients with heart failure with preserved ejection fraction (HFpEF) develop secondary pulmonary hypertension (PH) and subsequent right ventricular (RV) failure. The underlying mechanisms are not well understood, but involve passive congestion, active vascular remodeling with impaired pulmonary gas exchange and systemic activation of the immune system. Here, we propose a mechanistic interdependence of these processes, in that active recruitment of immune cells into the lung´s perivascular space drives lung vascular remodeling thus impairing pulmonary gas exchange. The ensuing systemic hypoxemia will in turn promote systemic inflammation and accelerate the decline in left ventricular (LV) and right ventricular (RV) function.

Homepage SFBs 1470

Project lead: Jana Grune, Wolfgang M. Kübler

Staff: Paul-Lennard Perret, Annika Winkler

The project deals with age-associated disease processes and their influence on the development of pulmonary hypertension. It was recently shown that the mean age of patients with pulmonary hypertension increases.

A typical change in blood vessels with age is a decrease in elasticity (loss of compliance) and increased growth of the vessel walls (hypertrophy). Since these mechanisms also play a disease-causing role in the pathogenesis of pulmonary hypertension, this project focuses on the investigation of the anti-aging protein Klotho, which has been demonstrated with declining plasma concentrations in the aging organism.

Project lead: Jana Grune, Bianca Nitzsche

Staff: Niklas Hegemann, Judith Rees

As part of preclinical research efforts concerning heart failure more than 200.000 animals have been sacrificed in Germany during 2021. The current project aims at continuous development of (animal-free) alternative methods for cardiovascular research to reduce the required animal numbers or ideally replace animal testing entirely. Central to our efforts is the evaluation of cardiac function of the incubated chicken egg using echocardiography (ultrasound examination of the heart) and performing electrocardiograms (evaluation of the electrical activity of the heart). The primary goal is to establish methodological routines for the aforementioned examinations and to validate them for application in cardiovascular research. In the next step, common cardiac disorders will be simulated in the incubated chicken egg using selected pharmacological agents and subsequently evaluated using our validated methods. Finally, we plan to implement the chicken egg model into ongoing and currently planned preclinical studies involving small animals (commonly mice and rats) to replace and reduce animal numbers. Initially, this project had been kickstarted in the Institute of Physiology with funding from the Charité 3R initiative and will now be continued by the recently founded research lab of Dr. Jana Grune.

Project lead: Jana Grune

Staff: David Faidel, Annika Winkler, Leonardo von der Ohe, Paul Neumann

Pulmonary hypertension (PH) is a frequent complication in heart failure patients, causing shortness of breath, fatigue, weakness, and syncope. Yet, no effective treatment is presently available, which is, at least in part, due to a lack of mechanistic understanding of the disease. The project aims to investigate aldosterone as a driver of pulmonary vascular remodelling, a key pathophysiological feature of pulmonary hypertension.