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

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

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)23-34
Number of pages12
JournalExperimental and Molecular Medicine
Issue number1
Publication statusPublished - 2022 Jan

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (grants 2019R1A2C3007142 to Y.G.K. and 2017M3A9B3061954 to H.J.P.).

Publisher Copyright:
© 2021, The Author(s).

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry


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