EGR1 Is Implicated in Right Ventricular Cardiac Remodeling Associated with Pulmonary Hypertension

Biology

Felicitas Oberndorfer¹  Andreas Zuckermann²  Michael Mildner³  Bahar Golabi³  Nika Skoro-Sajer⁴  Christian Gerges⁴  Irene Lang⁴  Philipp Hacker⁵  Bernhard Moser⁶  Maria Laggner⁶  Hendrik Jan Ankersmit⁶  Shahrokh Taghavi⁶  Peter Jaksch⁶  Jonas Bauer⁶ 

[1] Clinical Institute of Pathology, Medical University of Vienna, 1090 Vienna, Austria;Department of Cardiology, Medical University of Vienna, 1090 Vienna, Austria;Department of Dermatology, Medical University of Vienna, 1090 Vienna, Austria;Department of Medicine II, Division of Cardiology, Medical University of Vienna, 1090 Vienna, Austria;Department of Oral and Maxillofacial Surgery, University Hospital St. Poelten, 3100 St. Poelten, Austria;Department of Thoracic Surgery, Medical University of Vienna, 1090 Vienna, Austria;

关键词: pulmonary hypertension;    chronic thromboembolic pulmonary hypertension;    idiopathic pulmonary arterial hypertension;    right ventricular hypertrophy;    reverse right ventricular remodeling;    lung transplantation;   

DOI  :  10.3390/biology11050677

来源: DOAJ

【 摘 要 】

Background: Pulmonary hypertension (PH) is a vasoconstrictive disease characterized by elevated mean pulmonary arterial pressure (mPAP) at rest. Idiopathic pulmonary arterial hypertension (iPAH) and chronic thromboembolic pulmonary hypertension (CTEPH) represent two distinct subtypes of PH. Persisting PH leads to right ventricular (RV) hypertrophy, heart failure, and death. RV performance predicts survival and surgical interventions re-establishing physiological mPAP reverse cardiac remodeling. Nonetheless, a considerable number of PH patients are deemed inoperable. The underlying mechanism(s) governing cardiac regeneration, however, remain largely elusive. Methods: In a longitudinal approach, we profiled the transcriptional landscapes of hypertrophic RVs and recovered hearts 3 months after surgery of iPAH and CTEPH patients. Results: Genes associated with cellular responses to inflammatory stimuli and metal ions were downregulated, and cardiac muscle tissue development was induced in iPAH after recovery. In CTEPH patients, genes related to muscle cell development were decreased, and genes governing cardiac conduction were upregulated in RVs following regeneration. Intriguingly, early growth response 1 (EGR1), a profibrotic regulator, was identified as a major transcription factor of hypertrophic RVs in iPAH and CTEPH. A histological assessment confirmed our biocomputational results, and suggested a pivotal role for EGR1 in RV vasculopathy. Conclusion: Our findings improved our understanding of the molecular events driving reverse cardiac remodeling following surgery. EGR1 might represent a promising candidate for targeted therapy of PH patients not eligible for surgical treatment.

【 授权许可】

Unknown