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Effect of the haeme oxygenase-1/endogenous carbon monoxide system on atherosclerotic plaque formation in rabbits.

Liu DN, Fang Y, Wu LR, Liu XD, Li P, He ZY - Cardiovasc J Afr (2010 Sep-Oct)

Bottom Line: However, no significant differences were observed among the three experimental groups (p > 0.01).Compared with the Ch group, CO production and HO-1 activity increased markedly, while aortic HO activity and CO production decreased significantly in the Hm group.Compared with the Ch group, aortic endothlin-1 expression in the Hm group reduced significantly, while in the Zn group it was significantly higher than in the Ch group (p < 0.01).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiology, Guiyang Medical College, Guiyang, China. yi_yi0809@126.com

ABSTRACT

Background: To investigate the effect of the haeme oxygenase-1/carbon monoxide (HO-1/CO) system on atherosclerotic plaque formation and its possible mechanism.

Methods: For 12 weeks, rabbits were given a 1.5% cholesterol diet (Ch group, n = 8) or a 1.5% cholesterol diet plus an HO-1 inducer, haemin (Hm group, n = 8), or an HO-1 inhibitor, zinc protoporphyrin IX (Znpp-IX, Zn group, n = 8) by intraperitoneal injection.

Results: Compared with the normal control group (C group, n = 8), serum levels of lipids and oxidised low-density lipoproteins (ox-LDL) increased significantly in all experimental groups (p < 0.01). However, no significant differences were observed among the three experimental groups (p > 0.01). Compared with the control group, aortic nitric oxide (NO) production and nitric oxide synthase (cNOS) activity decreased markedly, whereas carbon monoxide (CO) production and HO-1 activity increased markedly in the Ch group (p < 0.01). This was associated with an increase in the area of aortic plaque of 54.00 ± 4.16%. Compared with the Ch group, CO production and HO-1 activity increased markedly, while aortic HO activity and CO production decreased significantly in the Hm group. The area of aortic plaque was significantly reduced in the Hm group (17.88 ± 3.01%), whereas the area of aortic plaque was significantly increased in the Zn group (61.13 ± 3.50%). Compared with the Ch group, aortic endothlin-1 expression in the Hm group reduced significantly, while in the Zn group it was significantly higher than in the Ch group (p < 0.01).

Conclusion: The HO-1/CO system plays an inhibitory role in atherosclerotic plaque formation. This role was not mediated by regulating serum lipids and ox-LDL, but was related to the reciprocal relationship between the HO-1/CO and NOS/NO systems in atherosclerosis and the down-regulated expression of endothlin-1 (ET-1), which inhibits the proliferation of vascular smooth muscle cells.

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Levels of HO -1 (left) and ET-1 (right) mRNA expression in the aorta. M: marker, C, Zn, Ch and Hm groups.
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Figure 4: Levels of HO -1 (left) and ET-1 (right) mRNA expression in the aorta. M: marker, C, Zn, Ch and Hm groups.

Mentions: As shown in Figs 2 and 4, HO-1 was mainly expressed in the aortic endothelial cells, foam cells and smooth muscle cells. In the C group, a small number of positive cells were distributed in the tunica–intima. HO-1 was expressed in the endothelial cells. In the Zn group, there were only a few positive cells, and HO-1 was occasionally expressed in the endothelial and foam cells in plaques. The expression rate of HO-1 was significantly lower than in the C group (14.15 ± 1.12 vs 19.02 ± 1.28%, p < 0.01).


Effect of the haeme oxygenase-1/endogenous carbon monoxide system on atherosclerotic plaque formation in rabbits.

Liu DN, Fang Y, Wu LR, Liu XD, Li P, He ZY - Cardiovasc J Afr (2010 Sep-Oct)

Levels of HO -1 (left) and ET-1 (right) mRNA expression in the aorta. M: marker, C, Zn, Ch and Hm groups.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3721901&req=5

Figure 4: Levels of HO -1 (left) and ET-1 (right) mRNA expression in the aorta. M: marker, C, Zn, Ch and Hm groups.
Mentions: As shown in Figs 2 and 4, HO-1 was mainly expressed in the aortic endothelial cells, foam cells and smooth muscle cells. In the C group, a small number of positive cells were distributed in the tunica–intima. HO-1 was expressed in the endothelial cells. In the Zn group, there were only a few positive cells, and HO-1 was occasionally expressed in the endothelial and foam cells in plaques. The expression rate of HO-1 was significantly lower than in the C group (14.15 ± 1.12 vs 19.02 ± 1.28%, p < 0.01).

Bottom Line: However, no significant differences were observed among the three experimental groups (p > 0.01).Compared with the Ch group, CO production and HO-1 activity increased markedly, while aortic HO activity and CO production decreased significantly in the Hm group.Compared with the Ch group, aortic endothlin-1 expression in the Hm group reduced significantly, while in the Zn group it was significantly higher than in the Ch group (p < 0.01).

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiology, Guiyang Medical College, Guiyang, China. yi_yi0809@126.com

ABSTRACT

Background: To investigate the effect of the haeme oxygenase-1/carbon monoxide (HO-1/CO) system on atherosclerotic plaque formation and its possible mechanism.

Methods: For 12 weeks, rabbits were given a 1.5% cholesterol diet (Ch group, n = 8) or a 1.5% cholesterol diet plus an HO-1 inducer, haemin (Hm group, n = 8), or an HO-1 inhibitor, zinc protoporphyrin IX (Znpp-IX, Zn group, n = 8) by intraperitoneal injection.

Results: Compared with the normal control group (C group, n = 8), serum levels of lipids and oxidised low-density lipoproteins (ox-LDL) increased significantly in all experimental groups (p < 0.01). However, no significant differences were observed among the three experimental groups (p > 0.01). Compared with the control group, aortic nitric oxide (NO) production and nitric oxide synthase (cNOS) activity decreased markedly, whereas carbon monoxide (CO) production and HO-1 activity increased markedly in the Ch group (p < 0.01). This was associated with an increase in the area of aortic plaque of 54.00 ± 4.16%. Compared with the Ch group, CO production and HO-1 activity increased markedly, while aortic HO activity and CO production decreased significantly in the Hm group. The area of aortic plaque was significantly reduced in the Hm group (17.88 ± 3.01%), whereas the area of aortic plaque was significantly increased in the Zn group (61.13 ± 3.50%). Compared with the Ch group, aortic endothlin-1 expression in the Hm group reduced significantly, while in the Zn group it was significantly higher than in the Ch group (p < 0.01).

Conclusion: The HO-1/CO system plays an inhibitory role in atherosclerotic plaque formation. This role was not mediated by regulating serum lipids and ox-LDL, but was related to the reciprocal relationship between the HO-1/CO and NOS/NO systems in atherosclerosis and the down-regulated expression of endothlin-1 (ET-1), which inhibits the proliferation of vascular smooth muscle cells.

Show MeSH
Related in: MedlinePlus