Endogenous hydrogen sulfide and ERK1/2-STAT3 signaling pathway may participate in the association between homocysteine and hypertension.

Figures

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  Figure 1.. Linear regression analysis on relationship between logarithm of blood pressure and Hcy level. Hcy: homocysteine; SBP: systolic blood pressure.

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  Figure 2.. Final SBP levels in all three groupings of Wistar and SHR rats. At the end of the study, Wistar rats in the Hcy group had a higher SBP than did the control group; additionally, SBP was lowest in the folate group (F = 3.956, P = 0.038). For SHR rats the folate group had the lowest SBP (t = 3.386, P = 0.010). For both types of rats, compared with the control group, SBP increased in the Hcy group and decreased after the addition of folic acid in the diet. *P = 0.010. Hcy: homocysteine; SBP: systolic blood pressure; SHR: spontaneously hypertensive rats.

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  Figure 3.. Homocysteine levels at baseline and final for Wistar and SHR rats. On concluding the animal studies, a significant increase in homocysteine was shown in both the Wistar Hcy rats (t = 3.063, P = 0.028) and the SHR Hcy rats (t = 2.525, P = 0.035) and both groups developed hyperhomocysteinemia after eight weeks of being fed the high methionine diet, *P < 0.05. Hcy: homocysteine; SHR: spontaneously hypertensive rats.

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  Figure 4.. Final hydrogen sulfide levels in the Wistar rat groups. Compared with the Wistar-control group, serum hydrogen sulfide levels in the Wistar Hcy group decreased after the 8-week methionine diet, and increased after the 4-week folate treatment. Hcy: homocysteine; **P = 0.002.

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  Figure 5.. Real-time PCR of CSE mRNA in rat kidney tissue in each group of Wistar and SHR rats. For SHR rats, expression of CSE mRNA in kidney tissue isolated from the folate group was significantly enhanced (F = 6.302, P = 0.008), while in Wistar rats, mRNA expression of CSE in the folate group was also enhanced, although the difference was not statistically significant. CSE: cystathionine γ-lyase; SHR: spontaneously hypertensive rats.

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  Figure 6.. Immunohistochemical staining of rat aorta in all three groupings of Wistar (A–C) and SHR (D–E) rats. Immunohistochemical staining of rat aorta showed that expression of CSE was identified in the smooth muscle layer of the artery wall but not in the endothelial layer. The vascular smooth muscle layers in both Hcy groups were significantly thickened. The scale of the figure is 1: 100 µm. CSE: cystathionine γ-lyase; Hcy: homocysteine; SHR: spontaneously hypertensive rats.

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  Figure 7.. Expression of ACE in rat kidney tissue for Wistar and SHR groups. Expression of ACE in rat kidney tissue showed that for Wistar rats, compared to the control group, ACE expression in the Hcy group was enhanced (t = –4.206, **P = 0.002) and in the folate group it was suppressed (t = 2.453, *P = 0.043). For SHRs this trend was similar but the difference was not statistically significant. ACE: angiotensin-converting enzyme; SHR: spontaneously hypertensive rats.

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  Figure 8.. Results of AGTR1/GAPDH levels using western blot for all groups of Wistar and SHR rats. Western blot revealed that compared to the Wistar groups the expression of AGTR1 in the corresponding SHR groups decreased. *P = 0.022. AGTR1: angiotensin II receptor type 1; SHR: spontaneously hypertensive rats.

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  Figure 9.. Expression of ACE mRNA (A) and AGTR1 mRNA (B) in fibroblasts stimulated by Hcy of 100 µmol/L for different times. Compared with the control group, *P < 0.05. ACE: angiotensin-converting enzyme; AGTR1: angiotensin II receptor type 1; CTL: control.

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  Figure 10.. The expression of ACE promoted by Hcy at different concentration of 0 µmol/L, 50 µmol/L, 100 µmol/L and 200 µmol/L. Control: the Hcy in the control group was 0 µmol/L. ACE: angiotensin-converting enzyme; Hcy: homocysteine.

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  Figure 11.. With the increase of concentration (A) and treated time (B) of Hcy, the expression of collagen type 1 and AGTR1 increased, and the maximal effect appears at Hcy concentration of 100 µmol/L and at 48 h of stimulation. *P < 0.05. AGTR1: angiotensin II receptor type 1; Hcy: homocysteine.

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  Figure 12.. With the increase of Hcy stimulation concentration, the expression levels of p-ERK1/2 and p-STAT3 were gradually increased, and the total expression of p-ERK1/2 (A) and p-STAT3 (B) in different groups were statistically significant. Compared with the control group, the expression of p-ERK1/2 and p-STAT3 reached the maximum at the Hcy concentration of 100 µmol/L and then gradually decreased. *P < 0.05. Hcy: homocysteine.