Continuous Infusion of Angiotensin IV Protects against Acute Myocardial Infarction via the Inhibition of Inflammation and Autophagy

Figures

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  Figure 1. Ang IV increased survive rate after MI without any effect on lipid levels. (a) MI induced high mortality in mice, while Ang IV increased the survive rate after MI. (b) There was no significant differences in lipid levels in 4 groups of mice. D: days; TC: total cholesterol; TG: triglycerides; LDL: low-density lipoprotein cholesterol; HDL: high-density lipoprotein cholesterol; Ang: angiotensin; MI: myocardial infarction. ∗P < 0.05.

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  Figure 2. Ang IV reduced MI-induced inflammatory response in mice. (a–c) Ang IV reduced MI-induced mRNA expression of inflammatory cytokines, including MCP-1, ICAM-1, and iNOS. (d–g) Ang IV reduced MI-induced protein expression of inflammatory cytokines. MCP-1: monocyte chemotactic protein 1; ICAM-1: intercellular adhesion molecule 1; iNOS: inducible nitric oxide synthase; Ang: angiotensin; MI: myocardial infarction. ∗P < 0.05 vs. the sham group; #P < 0.05 vs. the MI group.

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  Figure 3. Ang IV reduced apoptosis and autophagosomes in MI mice heart. (a, b) TUNEL staining showed that Ang IV reduced MI-induced cardiomyocyte apoptosis. Bar = 20 μm. (c) Transmission electron microscopy showed that MI induced autophagosomes and mitochondrial swelling and disarrangement, while Ang IV infusion could improve it. Bar = 0.5 μm. Ang: angiotensin; MI: myocardial infarction. ∗P < 0.05 vs. the sham group; #P < 0.05 vs. the MI group. Arrow, autophagosomes; cross, mitochondrial.

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  Figure 4. Ang IV improved cardiac function after MI in mice. (a) MI increased the HW and the ratio of HW/BW, while infusion of Ang IV reduced them. (b–d) Echocardiography showed that Ang IV improved cardiac function after MI, including EF, FS, LVEDs, and LVEDd. Ang: angiotensin; MI: myocardial infarction; HW: heart weight (g); BW: body weight (g); EF: ejection fraction; FS: fractional shortening; LVEDs: left ventricular end systolic internal diameter; LVEDd: left ventricular end diastolic internal diameter. ∗P < 0.05 vs. the sham group; #P < 0.05 vs. the MI group.

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  Figure 5. Ang IV reduced infarct size and fibrosis after MI in mice. (a, c) H&E staining showed that Ang IV infusion reduced MI-induced infarct size. Bar = 2 cm; (b, d) Masson staining showed that Ang IV infusion reduced MI-induced cardiac fibrosis. Bar = 50 μm. Ang: angiotensin; MI: myocardial infarction; ∗P < 0.05 vs. the sham group; #P < 0.05 vs. the MI group.

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  Figure 6. Ang IV reduced hypoxia-induced oxidative stress and DNA damage as well as inflammatory cytokine secretion in NRVCs. (a, b) DHE staining showed that pretreatment of Ang IV reduced oxidative stress. (c, d) Comet assay showed that Ang IV reduced hypoxia-induced DNA damage. (e, f) ELISA showed that Ang IV reduced hypoxia-induced TNF-ɑ and IL-1β secretion in supernatant. Ang: angiotensin; TNF-ɑ: tumor necrosis factor ɑ; IL-1β: interleukin 1β; NRVCs: the neonatal rat ventricular myocytes. ∗P < 0.05 vs. the control group; #P < 0.05 vs. the hypoxia group.

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  Figure 7. Ang IV reduced hypoxia-induced apoptosis and autophagy in NRVCs. (a, b) TUNEL staining showed that Ang IV reduced hypoxia-induced cardiomyocyte apoptosis. Bar = 100 μm. (c, d) Western blot analysis showed that Ang IV reduced the transformation of LC3-I to LC3-II but increased p62 expression. Ang: angiotensin; NRVCs: the neonatal rat ventricular myocytes. DAPI: blue; TUNEL: green; ∗P < 0.05 vs. the control group; #P < 0.05 vs. the hypoxia group.