Guo-Wei He

TEDA International Cardiovascular Hospital, Tianjin University, China

Title: Post-Translational Acylation of Proteins in Cardiovascular Diseases

Biography

Guo-Wei He is a Distinguished Professor of Tianjin University, China and Academician (Foreign Correspondence Member) at The National Academy of Medicine, France (2019-); Vice President & Senior Cardiac Surgeon at TEDA International Cardiovascular Hospital, Tianjin University; Clinical Professor of Surgery at Oregon Health & Science University, Portland, OR, USA (2003-); 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.

He was Chair Professor of Cardiothoracic Surgery, University of Hong Kong, 1995-2000 and Research Chair Professor, Chinese University of Hong Kong (2000-2009). He was Director of Cardiovasc Res Lab, St, Vincent Hospital, Portland, OR, U.S.A. (1994-2012). He is an active cardiac surgeon and he performed more than 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 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.  He published 430 articles/reports in SCI-index international journals. He ranks in World's Top 2% Scientists (2019-2024) with Google scholar citation > 10,000 and  H-index of top 1%. He ranks world’s Top 1% in Medicine, Chemistry, Genetics and Molecular Biology. Highly-cited Chinese scholar (2024). The top 0.05% of all scholars worldwide (ScholarGPS).

Abstract

Background: Acylations are post-translational modifications (PTMs), in which functional groups are attached to amino acids on proteins. Most acylations (acetylation, crotonylation, succinylation, propionylation, butyrylation, lactylation and malonylation) involve lysine. Acylations have important roles in physiological and pathophysiological processes, including cardiovascular diseases.

Methods: PTM proteomics was applied in the human cardiovascular tissues for PTM studies in 1) the human atrial tissue from atrial fibrillation (AF) patients with heart valve disease during cardiac surgery for lysine 2-hydroxyisobutyrylation (Khib) sites and 2)  paired internal thoracic artery (ITA) and saphenous vein (SV) segments (n=150) from patients undergoing CABG surgery for lysine crotonylation (Kcro). The functional changes of differential modification sites were further validated at the cellular level.

Results: 1) The modification of 124 Khib sites in 35 proteins and 67 sites in 48 proteins exhibited significant increase or decrease in AF. Ten Khib sites were included in energy metabolism-related signaling. Decreased HXK1 K418hib regulated by HDAC2 attenuated the original chemical binding domain between HXK1 and glucose, inhibited the binding ability between HXK1 and glucose, and reduced catalytic ability of the enzyme, resulting in low production of glucose-6-phosphate and ATP. Further, it also increased Kir6.2 protein and the current of KATP channel, and decreased APD.

2) 3,652 proteins are differentially-expressed and 411 proteins are differentially-crotonylated in ITA/SV segments. SV showed higher crotonylation levels on TXN-K3, GLO1-K157, and GAPDH-K61, associated with decreased enzymatic activity, elevated methylglyoxal (MGO) accumulation, and increased oxidative stress.

Conclusions: These studies for the first time demonstrate the importance of Khib to catalysis of HXK1 and reveals molecular mechanisms of HXK1 K418hib in AF and to reveal significant differences in PTM crotonylation between human ITA and SV. These studies emphasize the importance of PTM in cardiovascular diseases, providing new insight into the mechanism of the pathophysiology of the disease.