Abstract:
Heart failure (HF) is often a result of cardiac hypertrophy, and it is still the main public health challenge. Although vericiguat has been proved to be effective in treating heart failure through soluble guanylate cyclase (sGC), its potential preventive effects on myocardial hypertrophy and the exact related mechanisms are still unclear. We aimed to investigate the mechanism of the effectiveness of vericiguat in treating HF, focusing on its multi-targets of therapeutic effect. Echocardiographic assessments performed after treatment of vericiguat revealed significant improvements in cardiac function compared to untreated controls (TAC+SS). Biochemically, vericiguat effectively reversed the decrease of cGMP levels observed in hypertrophic mice hearts. Histological analysis showed that hypertrophy and fibrosis were reduced, myofibril arrangement, mitochondrial function and autophagy were improved, and the swelling of the sarcoplasmic reticulum was reduced. This study for the first time demonstrates that in addition to the direct effect of cGMP signaling, vericiguat may target and regulate HDAC1 expression and may repair sarcoplasmic reticulum swelling and enhance autophagy in hypertrophic hearts. We conclude that the preventive effect of vericiguat on the HF through multiple mechanisms and the results emphasize the potential clinical usefulness of vericiguat in the prevention of the progress of HF.
Biography:
Professor Guo-Wei HE, MD, PhD, DSc, is Distinguished Professor of Tianjin University, China and Academician (Foreign Correspondence Member) at The National Academy of Medicine, France (2019-). Professor He is Vice President & Senior Cardiac Surgeon at TEDA International Cardiovascular Hospital, Tianjin University and Director of Institute for Cardiovasc Diseases, Tianjin University & Chinese Academy of Medical Sciences. He also holds Clinical Professor of Surgery at Oregon Health & Science University, Portland, OR, USA (2003-). In addition, Professor He is Director, Branch Center for National Clinical Research Center for Cardiovascular Disease and Director of Tianjin Key Laboratory for Molecular Regulation and Translational Medicine of Cardiovascular Diseases. He obtained Doctor of Science (2003) and Ph. D.(1989) from Monash University, Melbourne, Australia.
Professor He was Chair Professor of Cardiothoracic Surgery, University of Hong Kong, 1995-2000 and Research Chair Professor, Chinese University of Hong Kong (2000-2009). Professor He was Director of Cardiovasc Res Lab, St, Vincent Hospital, Portland, OR, U.S.A. (1994-2012). Professor He is an active cardiac surgeon and he performed about 8,000 open heart operations. Notably, he is the first surgeon performing radial artery plus internal mammary artery in CABG at University of Hong Kong in Asia (1995) and is well known for “He Classification” and “He solutions” for CABG grafts. Apart from clinical practice, he is an active research on basic science at the molecular (genetic and protein) level and obtained more than 80 research grants and awards such as First Class Award, Tianjin Municipal Natural Science Award (2012), First Class Award, Prize of Science & Technology, The China Medicine Education Association (2021), exec. Professor He has supervised PhD students and postdoc for more than 30 years.
