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Published on: August 14, 2019
Isosorbide mononitrate promotes angiogenesis in embryonic development of zebrafish
Hui Lv1, Bo Liu2, Yongwen Qin3
1The Second Affiliated Hospital of ShanXi Medical University, Department of Cardiovascular Disease, Taiyuan, Shanxi, 030001, China.
Insights
Isosorbide mononitrate (ISMN) promotes blood vessel growth (angiogenesis) in zebrafish embryos and human cells. This suggests ISMN could be a potential therapeutic for diseases linked to poor blood vessel formation.
Area of Science:
- Cardiovascular Medicine
- Molecular Biology
- Developmental Biology
Background:
- Coronary heart disease (CHD) is a major global health concern.
- Angiogenesis, the formation of new blood vessels, is critical in CHD.
- The angiogenic effects of common cardiovascular drugs are not fully understood.
Purpose of the Study:
- To investigate the angiogenic efficacy of four cardiovascular medications: aspirin, pravastatin, metoprolol, and isosorbide mononitrate (ISMN).
- To elucidate the underlying molecular mechanisms of ISMN-induced angiogenesis.
Main Methods:
- Zebrafish embryos were immersed in solutions of the four drugs to assess angiogenesis by measuring intersegmental vessel (ISV) length and number.
- In vitro experiments using human umbilical vein endothelial cells (HUVECs) were conducted to evaluate cell viability, proliferation, apoptosis, and the expression of angiogenesis-related genes and microRNAs (miRNAs).
Main Results:
- ISMN significantly increased the length and number of ISVs in zebrafish embryos.
- ISMN enhanced HUVEC viability and proliferation while reducing apoptosis.
- ISMN elevated the expression of angiogenesis-related genes (vegf, kdrl, pdgfr) in zebrafish embryos and regulated specific miRNAs (miR-126, miR-130a, miR-210) in HUVECs.
Conclusions:
- ISMN demonstrates pro-angiogenic properties in both zebrafish embryos and human endothelial cells.
- ISMN's mechanism involves promoting cell viability and proliferation and modulating key angiogenic gene and miRNA expression.
- ISMN holds potential as a therapeutic agent for angiogenesis-related diseases.
Abstract:
Coronary heart disease (CHD) is a leading cause of death worldwide, and angiogenesis plays important roles in CHD. Thus, in the present study, the angiogenic efficacy of four common cardiovascular medicines (aspirin, pravastatin, metoprolol and isosorbide mononitrate (ISMN)) was determined by the number and length of zebrafish intersegmental vessels (ISVs) after immersing zebrafish embryos in different medicines. Results showed that ISMN significantly increased the length and number of ISVs. ISMN is a long-acting nitrate ester drug. It has been used as a vasodilator to dilate arteries and veins to reduce the cardiac preload and postload. However, the effect of ISMN on angiogenesis remains unclear. Thus, by in vitro experiments, the angiogenic mechanism of ISMN was evaluated through detecting the viability and proliferation of human umbilical vein endothelial cells (HUVECs) and the expression of angiogenesis-related genes and miRNAs. Results indicated that ISMN could increase the viability and proliferation of HUVECs by decreasing apoptosis, and elevated the expressions of vedf, kdrl, pdgfr in zebrafish embryos. Furthermore, the expressions of miR-126, miR-130a and miR-210 were also regulated in ISMN-treated HUVECs. In conclusion, ISMN could promote angiogenesis in zebrafish embryos and HUVECs, implying ISMN may be a potential therapeutic in treating angiogenesis-related diseases.
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