Frontiers in Cardiovascular Medicine (Apr 2022)
Artificial Intelligence Uncovers Natural MMP Inhibitor Crocin as a Potential Treatment of Thoracic Aortic Aneurysm and Dissection
- Feiran Qi,
- Feiran Qi,
- Feiran Qi,
- Feiran Qi,
- Yan Liu,
- Yan Liu,
- Yan Liu,
- Yan Liu,
- Kunlin Zhang,
- Kunlin Zhang,
- Kunlin Zhang,
- Yanzhenzi Zhang,
- Yanzhenzi Zhang,
- Yanzhenzi Zhang,
- Yanzhenzi Zhang,
- Ke Xu,
- Ke Xu,
- Ke Xu,
- Ke Xu,
- Mei Zhou,
- Huinan Zhao,
- Huinan Zhao,
- Huinan Zhao,
- Huinan Zhao,
- Shuolin Zhu,
- Shuolin Zhu,
- Shuolin Zhu,
- Shuolin Zhu,
- Jianxin Chen,
- Ping Li,
- Ping Li,
- Ping Li,
- Ping Li,
- Jie Du,
- Jie Du,
- Jie Du,
- Jie Du
Affiliations
- Feiran Qi
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Feiran Qi
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Feiran Qi
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Feiran Qi
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Yan Liu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Yan Liu
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Yan Liu
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Yan Liu
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Kunlin Zhang
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Kunlin Zhang
- CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
- Kunlin Zhang
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
- Yanzhenzi Zhang
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Yanzhenzi Zhang
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Yanzhenzi Zhang
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Yanzhenzi Zhang
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Ke Xu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Ke Xu
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Ke Xu
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Ke Xu
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Mei Zhou
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China
- Huinan Zhao
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Huinan Zhao
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Huinan Zhao
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Huinan Zhao
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Shuolin Zhu
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Shuolin Zhu
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Shuolin Zhu
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Shuolin Zhu
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Jianxin Chen
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China
- Ping Li
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Ping Li
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Ping Li
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Ping Li
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- Jie Du
- Beijing Anzhen Hospital, Capital Medical University, Beijing, China
- Jie Du
- Beijing Institute of Heart Lung and Blood Vessel Diseases, Beijing, China
- Jie Du
- Beijing Collaborative Innovation Centre for Cardiovascular Disorders, Beijing, China
- Jie Du
- The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing, China
- DOI
- https://doi.org/10.3389/fcvm.2022.871486
- Journal volume & issue
-
Vol. 9
Abstract
Thoracic aortic aneurysm and dissection (TAAD) is a lethal cardiovascular condition without effective pharmaceutical therapy. Identifying novel drugs that target the key pathogenetic components is an urgent need. Bioinformatics analysis of pathological studies indicated “extracellular matrix organization” as the most significant functional pathway related to TAAD, in which matrix metallopeptidase (MMP) 2 and MMP9 ranked above other proteases. MMP1-14 were designated as the prototype molecules for docking against PubChem Compound Database using Surflex-Dock, and nine natural compounds were identified. Using a generic MMP activity assay and an aminopropionitrile (BAPN)-induced TAAD mouse model, we identified crocin as an effective MMP inhibitor, suppressing the occurrence and rupture of TAAD. Biolayer interferometry and AI/bioinformatics analyses indicated that crocin may inhibit MMP2 activity by direct binding. Possible binding sites were investigated. Overall, the integration of artificial intelligence and functional experiments identified crocin as an MMP inhibitor with strong therapeutic potential.
Keywords
- thoracic aortic aneurysm and dissection
- drug therapy
- matrix metallopeptidase
- crocin
- natural compound
- artificial intelligence
