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Zhang H, Kim H, Park BW, et al. CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury. Exp Mol Med. 2022;doi: 10.1038/s12276-021-00720-w.
Zhang, H., Kim, H., Park, B. W., Noh, M., Kim, Y., Park, J., Park, J. H., Kim, J. J., Sim, W. S., Ban, K., Park, H. J., & Kwon, Y. G. (2022). CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury. Experimental & molecular medicine, . https://doi.org/10.1038/s12276-021-00720-w
Zhang, Haiying, et al. "CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury." Experimental & molecular medicine vol. (2022). doi: https://doi.org/10.1038/s12276-021-00720-w
Zhang H, Kim H, Park BW, Noh M, Kim Y, Park J, Park JH, Kim JJ, Sim WS, Ban K, Park HJ, Kwon YG. CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury. Exp Mol Med. 2022 Jan 07; doi: 10.1038/s12276-021-00720-w. Epub 2022 Jan 07. PMID: 34997212.
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Exp Mol Med. 2022 Jan 07; doi: 10.1038/s12276-021-00720-w. Epub 2022 Jan 07.

CU06-1004 enhances vascular integrity and improves cardiac remodeling by suppressing edema and inflammation in myocardial ischemia-reperfusion injury.

Experimental & molecular medicine

Haiying Zhang, Hyeok Kim, Bong Woo Park, Minyoung Noh, Yeomyeong Kim, Jeongeun Park, Jae-Hyun Park, Jin-Ju Kim, Woo-Sup Sim, Kiwon Ban, Hun-Jun Park, Young-Guen Kwon

Affiliations

  1. Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea.
  2. R&D Department, Curacle Co. Ltd, Seongnam-si, Republic of Korea.
  3. Department of Medical Life Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea.
  4. Department of Biomedical Sciences, City University of Hong Kong, Kowloon Tong, 999077, Hong Kong.
  5. Department of Medical Life Science, College of Medicine, The Catholic University of Korea, Seoul, 06591, Republic of Korea. [email protected].
  6. Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea, Banpo-daero 222, Seocho-gu, Seoul, 137701, Republic of Korea. [email protected].
  7. Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, Republic of Korea. [email protected].

PMID: 34997212 DOI: 10.1038/s12276-021-00720-w

Abstract

Ischemia-reperfusion (I/R) injury accelerates the cardiomyocytes (CMs) death by oxidative stress, and thereby deteriorates cardiac function. There has been a paradigm shift in the therapeutic perspective more towards the prevention or amelioration of damage caused by reperfusion. Cardiac microvascular endothelial cells (CMECs) are more vulnerable to reperfusion injury and play the crucial roles more than CMs in the pathological process of early I/R injury. In this study, we investigate that CU06-1004, as a vascular leakage blocker, can improve cardiac function by inhibiting CMEC's hyperpermeability and subsequently reducing the neutrophil's plugging and infiltration in infarcted hearts. CU06-1004 was delivered intravenously 5 min before reperfusion and the rats were randomly divided into three groups: (1) vehicle, (2) low-CU06-1004 (1 mg/kg, twice at 24 h intervals), and (3) high-CU06-1004 (5 mg/kg, once before reperfusion). CU06-1004 treatment reduced necrotic size and cardiac edema by enhancing vascular integrity, as demonstrated by the presence of intact junction proteins on CMECs and surrounding pericytes in early I/R injury. It also decreased the expression of vascular cell adhesion molecule 1 (VCAM-1) on CMECs, resulting in reduced infiltration of neutrophils and macrophages. Echocardiography showed that the CU06-1004 treatment significantly improved cardiac function compared with the vehicle group. Interestingly, single high-dose treatment with CU06-1004 provided a greater functional improvement than repetitive low-dose treatment until 8 weeks post I/R. These findings demonstrate that CU06-1004 enhances vascular integrity and improves cardiac function by preventing lethal myocardial I/R injury. It can provide a promising therapeutic option, as potential adjunctive therapy to current reperfusion strategies.

© 2021. The Author(s).

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