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SFB 1213:  Pulmonary Hypertension and Cor Pulmonale

Subject Area Biology
Medicine
Term since 2016
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 268555672
 
Heart and lung diseases are the leading causes of death and represent the highest socio-economic burden of all diseases worldwide. Pulmonary hypertension (PH) is a progressive disease of multifactorial etiology with poor prognosis. Up to 100 million people are affected by its various subtypes. PH is characterized by pathological inward remodeling and a loss of patency of the lung vasculature. Thus challenged with increased afterload, the right ventricle (RV) initially responds to PH with a beneficial “adaptive” hypertrophy, which is, however, often rapidly followed by “maladaptive” changes, leading to right heart decompensation and failure, the ultimate cause of death in PH (cor pulmonale). The Collaborative Research Center (CRC1213) combines basic science approaches and bedside clinical research in a highly interactive network with the aim to elucidate the pathogenic sequelae underlying PH and cor pulmonale and to evaluate novel treatment concepts. We are pursuing an integrated concept to understand the common pathophysiological processes and molecular mechanisms that underlie the structural pulmonary vascular abnormalities as well as RV adaptation and maladaptation in PH. Prevention of RV maladaptation may open new ways to prevent death from PH. Our long-term aim is to reverse remodeling to regain physiological lung vascular structure and function and to develop RV-focused therapy, currently not available. The proposal has strong translational orientation: its projects span the entire spectrum from genetic/epigenetic signatures, molecular pathway mapping, cell and developmental biology, preclinical disease models, and in vivo molecular imaging, to clinical trials and registries/patient cohorts as well as extensive biobanking. The CRC1213 Faculty is very well prepared to fulfill this mission as documented by several groundbreaking contributions to lung vascular and cardiac research, and as evidenced by top ranking publications, coordination of large research consortia and translation of several key findings into clinical use and exploitation. As examples from the second funding period, we proved for that PH is indeed reversible and identified new drivers of PH: The mammalian Ste20-like kinases, the matricellular protein SPARC, and the NADPH oxidase subunit NoxO1. We found that loss of the histone-methyl-transferase Suv4-20h1 caused RV dilation in mice. Clinically, we defined a new cut-off to predict PH, which was implemented in the 2022 European guidelines for diagnosis and treatment of PH and we defined new PH biomarkers. Two new projects will enrich the CRC1213´s portfolio: One on PH in lung fibrosis basement membrane and matrix remodeling, and a second on the role and mechanism of atrial fibrillation in PH. Three projects were terminated. In addition to existing structural measures, the CRC will continue to support early career development of young basic and clinician scientists, as well as equal opportunities and diversity.
DFG Programme Collaborative Research Centres

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Applicant Institution Justus-Liebig-Universität Gießen
 
 

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