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. 2022 Sep 12;8(9):e10582.
doi: 10.1016/j.heliyon.2022.e10582. eCollection 2022 Sep.

Tumstatin (69-88) alleviates heart failure via attenuating oxidative stress in rats with myocardial infarction

Congfei Zhu  1 , Zhi Zuo  2 , Cheng Xu  1 , Mingyue Ji  1 , Junjie He  1 , Jinshuang Li  3
Affiliations

Tumstatin (69-88) alleviates heart failure via attenuating oxidative stress in rats with myocardial infarction

Congfei Zhu et al. Heliyon. .

Abstract

Background: This study aimed to elucidate the effects of tumstatin (69-88) on heart failure and the underlying mechanism.

Materials and methods: Myocardial infarction (MI) was induced by ligating the left coronary artery in rats to trigger heart failure.

Results: Tumstatin (69-88) can reduce cardiac insufficiency in rats with heart failure. The increased cardiac fibrosis in MI rat was attenuated by tumstatin (69-88). Increase of cardiac atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in rats with myocardial infarction, and Ang II-treated NRCMs or H9C2 cells was inhibited by tumstatin (69-88). In the heart of MI rats, and Ang II-treated NRCMs or H9C2 cells, the superoxide anions and NADPH oxidase (Nox) activity rose and the superoxide dismutase (SOD) activity was reduced, which was inhibited by tumstatin (69-88). Diethyldithiocarbamate, an SOD inhibitor, increased the ANP and BNP in NRCMs or H9C2 cells. Tumstatin (69-88) inhibited the Ang II-induced raises of ANP and BNP in NRCMs or H9C2 cells, which was reversed by DETC.

Conclusions: These results indicate that tumstatin (69-88) alleviates cardiac dysfunction of heart failure. Tumstatin (69-88) improves the hypertrophy of cardiomyocytes via attenuation of oxidative stress. Tumstatin (69-88) may be a potential drug for heart failure in the future.

Keywords: Heart failure; Myocardial infarction; Oxidative stress; Tumstatin (69–88).

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Tumstatin (69–88) attenuated cardiac dysfunction of myocardial infarction rats. Tumstatin (69–88) reversed the decreases of LVSP, LV + dp/dtmax, EF and FS, and the increases of LVEDP, LVVs, LVVd, LVIDs and LVIDd of myocardial infarction rats. n = 8 for each group. The results are expressed as mean ± SEM. ∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001.
Figure 2
Figure 2
Tumstatin (69–88) alleviated cardiac fibrosis of myocardial infarction rats. a, Tumstatin (69–88) alleviated the increase of myocardial fibrosis in rats with myocardial infarction using sirius red staining. b, Tumstatin (69–88) inhibited the increases of collagen I and III mRNA in the heart of myocardial infarction rats. c, Tumstatin (69–88) inhibited the raises of collagen I and III protein in the heart of myocardial infarction rats. n = 8 for each group. The uncropped versions of western blots used for the analysis are presented in Supplementary Figure 1.
Figure 3
Figure 3
Tumstatin (69–88) alleviated cardiac hypertrophy. a, Tumstatin (69–88) inhibited the raised ANP and BNP in the heart of myocardial infarction rats. b, Tumstatin (69–88) inhibited the Ang II-induced raises of ANP and BNP in neonatal rat cardiomyocytes (NRCMs). c, Tumstatin (69–88) inhibited the Ang II-induced raises of ANP and BNP in H9C2 cells. n = 8 for each group.
Figure 4
Figure 4
Tumstatin (69–88) attenuated oxidative stress of heart failure. a, Tumstatin (69–88) reversed the increased ROS level in the heart of myocardial infarction rats. b, Tumstatin (69–88) reversed the increased superoxide anions and Nox activity, and the decreased SOD activity in the heart of myocardial infarction rats. c, Tumstatin (69–88) reversed the Ang II-induced increases of superoxide anions and Nox activity, and the ecreased SOD activity in NRCMs. d, Tumstatin (69–88) reversed the Ang II-induced raises of superoxide anions and Nox activity, and the ecreased SOD activity in H9C2 cells. n = 8 for each group.
Figure 5
Figure 5
Effects of SOD inhibitor and antioxidant tiron on cardiomyocyte hypertrophy. a, SOD inhibitor DETC reversed the mitigation influences of tumstatin (69–88) on the raised ANP and BNP which were induced by Ang II in NRCMs. b, DETC reversed the alleviating effects of tumstatin (69–88) on the raises of ANP and BNP in H9C2 cells which were induced by Ang II. c, Antioxidant tiron inhibited the raises of ANP and BNP in NRCMs which were induced by Ang II. d, Tiron inhibited the raises of ANP and BNP in H9C2 cells which were induced by Ang II. n = 8 for each group.
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