Recently, Prof. Chen Yuguo, Prof. Wei Shujian and Prof. Xu Feng’s team, from the Department of Emergency and Chest Pain Center of Qilu Hospital of Shandong University, published a research paper entitled "Carbonylation of Runx2 at K176 by 4-hydroxynonenal Accelerates Vascular Calcification" in Circulation (IF=37.8). The study revealed a new mechanism in which the carbonylation modification of Runx2 by 4-hydroxynonenal (4-HNE) accelerates vascular calcification, while ALDH2 alleviates the progression of calcification by metabolizing 4-HNE. These findings provide a broader understanding of the prevention and treatment of vascular calcification. Postdoctoral Zhai Xiaoxuan and research associate Cao Shengchuan are co-first authors. Prof.Chen Yuguo, Prof.Wei Shujan and Prof.Xu Feng are co-corresponding authors. Qilu Hospital of Shandong University is the unique first authors' and corresponding authors' affiliation.

Vascular calcification refers to the abnormal deposition of calcium and phosphorus crystals in the blood vessel wall, which is considered to be an independent risk factor for morbidity and mortality of cardiovascular disease. It occurs in patients with chronic renal failure, diabetes, ageing and atherosclerosis commonly. The mechanism involved in vascular calcification is complex, and there is still a lack of effective treatment strategies for vascular calcification.

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme in the metabolism of ethanol and a variety of endogenous and exogenous toxic aldehydes. ALDH2 rs671 gene mutation is the most common functional gene mutation in the Chinese population. The research team found that 4-HNE increased in vascular calcification, and ALDH2 knockout accelerated vascular calcification, while ALDH2 overexpression or activation alleviated vascular calcification. It was also found that the ALDH2 rs671 gene mutation was related to more severe coronary artery calcification in patients with coronary heart disease. 4-HNE enhanced the stability of Runx2 by direct carbonylation of the K176 site of Runx2 and promoting vascular calcification. As the key metabolic enzyme of 4-HNE, ALDH2 may be an important potential target for the treatment of vascular calcification.

This work was supported by the National Natural Science Foundation of China,the National Key Research and Development Program of China and other projects.

Professor Chen Yuguo’s team has long been committed to the study of the role and mechanism of ALDH2 gene mutation and aldehydes and has proposed the theory of "aldehyde metabolism disorder" in the treatment of acute critical vascular diseases. They have achieved a series of high-level research outcomes. Several research papers have been published in authoritative journals, such as JAHA 2018, ATVB 2019, Atherosclerosis 2020, Eur Heart J 2020, JCI Insight 2021, ATVB 2022, Nature Reviews Cardiology 2023and Advanced Science 2023 (x2). In addition, they have won several provincial and ministerial awards, such as the first prize of Science and Technology Progress of the Ministry of Education, the first prize in Science and Technology Progress of Shandong Province and the first prize in the Chinese Medical Science and Technology Award.

Article Link：https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.123.065830