Expression of Lectin like Oxidized Low Density Lipoprotein Receptor-1 in the Spontaneous Hypertensive Rat with High Cholesterol Diet

Ki-Seok Kim; No Kwan Park; Song-Yi Kim; Dong-Woon Kim; Seung-Jae Joo; Myeong-Chan Cho

doi:10.5646/jksh.2011.17.2.57

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Kim, Park, Kim, Kim, Joo, and Cho: Expression of Lectin like Oxidized Low Density Lipoprotein Receptor-1 in the Spontaneous Hypertensive Rat with High Cholesterol Diet

Original Article

J Korean Soc Hypertens 2011;17(2):57-64.

Published online: 10 June 2011

DOI: https://doi.org/10.5646/jksh.2011.17.2.57

Expression of Lectin like Oxidized Low Density Lipoprotein Receptor-1 in the Spontaneous Hypertensive Rat with High Cholesterol Diet

Ki-Seok Kim, MD^1,, No Kwan Park, PhD², Song-Yi Kim, MD¹, Dong-Woon Kim, MD², Seung-Jae Joo, MD¹, Myeong-Chan Cho, MD²

¹Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea

²Department of Internal Medicine, Chungbuk National University School of Medicine, Cheongju, Korea

Tel: 064) 717-1481, Fax: 064) 757-8276 E-mail: kiseok@jejunu.ac.kr

Received 15 March 201120 June 2011 Accepted 22 June 2011

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background:

Lectin-like, oxidized, low-density lipoprotein receptorreceptors (LOX-1) recognizes recognize vascular oxidized low-density lipoprotein (LDL), which may play an important role in the pathogenesis of atherosclerosis. We investigated the expressions expression of LOX-1 and redox-regulating thyoredoxinthioredoxin systems in a hypertension and hypercholesterolemia rat model.

Methods:

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rat (WKY) rats were fed with a normal cholesterol diet (NC) and a high cholesterol diet (HC) for 4 weeks. Plasma LDL cholesterol levels and blood pressure were measured at 1 and 4 weeks. Histological changes of atherosclerosis in the vessel was evaluated by hematoxylin and eosin staining and immunocytochemistry. The expressions expression of LOX-1 and thyoredoixnthioredoxin were measured by Western western blot analysis.

Results:

In the SHR groupsgroup, blood pressure after 4 weeks was significantly higher than initial levels. LDL-cholesterol levels in the SHR-HC group were increased at 4 weeks (15.3 ± 2.6 mg/dL vs. 20.2 ± 2.6 mg/dL, p < 0.01) compared with the SHR-NC group. In oxyblot analysis, the degree of oxidative stress of in the SHR-HC group was significantly higher than in the SHR-NC group (p < 0.05). The expressions expression of LOX-1 and Trx were was significantly increased in the SHR-HC group compared with the SHR-NC group (p < 0.05) on western blot analysis. Focal overexpressions overexpression of LOX-1 were was observed at the intima layer of the thoracic aorta, and was which wereonly observed in the SHR-HC group.

Conclusions:

The expressions expression of LOX-1 and oxidative stress were was significantly increased in the “hypertension with hypercholesterol” rat model. These findings suggested suggest that LOX-1 and redox systems may play a certain role in development and progression of atherosclerosis.

Keywords: Atherosclerosis, Hypertension, Oxidative stress

References

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Fig. 1.

Change of blood pressure and left ventricular wall thickness. (A) SBP change at 4 weeks experiment; WKY-NC, WKY-HC vs. SHR-NC, SHR-HC, p<0.05. (B) Left ventricular wall thickness at 4 weeks experiment; WKY-NC, WKY-HC vs. SHR-NC, SHR-HC, p<0.05. SBP, systolic blood pressure; WKY, Wistar Kyoto rat; SHR, spontaneous hypertensive rat; NC, normal cholesterol diet; HC, high cholesterol diet; LDL, low density lipoprotein. n=5 in each group. *p<0.05.

Fig. 2.

Change of plasma low density lipoprotein levels. Plasma LDL level; WKY-NC vs. WKY-HC, SHR-NC, p<0.05, WKY-NC, WKY-HC, SHR-NC vs. SHR-HC, p<0.01, WKY: Wistar Kyoto rat, SHR: spontaneous hypertensive rat, NC: normal cholesterol diet, HC: high cholesterol diet, LDL: low density lipoprotein. n=5 in each group. *p<0.05, ^†p<0.01.

Fig. 3.

Expression patterns of oxidative stress in thoracic aorta. (A) Oxyblot analysis of thoracic aorta, WKY-NC vs. WKY-HC, SHR-NC, p<0.05, WKY-NC, WKY-HC, SHR-NC vs. SHR-HC, p<0.01. (B) Representative figure of oxyblot analysis. (C) Expression patterns of TRX in thoracic aorta on western blot analysis, WKY-NC vs. WKY-HC, SHR-NC, p<0.05, WKY-NC, WKY-HC, SHR-NC vs. SHR-HC, p<0.01. (D) Representative figure of western blot analysis of TRX. WKY, Wistar Kyoto rat; SHR, spontaneous hypertensive rat; NC, normal cholesterol diet; HC, high cholesterol diet; TRX, thioredoxin. n=3 in each group. *p<0.05, ^†p<0.01.

Fig. 4.

Expression patterns of lectin-like oxidized low-density lipoprotein receptor (LOX-1) in thoracic aorta. (A) Expression patterns of LOX-1 in thoracic aorta on western blot analysis, WKY-NC vs. WKY-HC, SHR-NC, p<0.05, WKY-NC, WKY-HC, SHR-NC vs. SHR-HC, p<0.01. (B) Representative figure of western blot analysis of LOX-1. WKY, Wistar Kyoto rat; SHR, Spontaneous hypertensive rat; NC, normal cholesterol diet; HC, high cholesterol diet. n=3 in each group. *p<0.05, ^†p<0.01.

Fig. 5.

Histological findings of thoracic aorta. (A-D) H&E stain findings of thoracic aorta. (E) Immunohistochemistry finding in SHR-HC group, white arrow tips indicated lectin-like oxidized low-density lipoprotein receptor expressions. WKY, Wistar Kyoto rat; SHR, spontaneous hypertensive rat; NC, normal cholesterol diet; HC, high cholesterol diet.

Table 1.

Baseline characteristics of blood pressure and left ventricle wall thickness

	Study period	WKY		SHR
	Study period	NC	HC	NC	HC
Body Weight (g)	1 wk	134.2 ± 4.3	136.7 ± 3.8	134.6 ± 4.5	137.3 ± 6.2
	4 wk	283.9 ± 7.2	276.9 ± 10.2	257.3 ± 9.8	281.2 ± 7.5
SBP (mm Hg)	1 wk	112.7 ± 13.2	107.1 ± 4.7	172.5 ± 16.1^†	173.6 ± 8.1^†
	4 wk	148.7 ± 8.1	136.6 ± 10.1	191.9 ± 16.6^†	195.3 ± 6.2^†
Wall thickness (mm)	1 wk	1.2 ± 0.2	1.2 ± 0.1	1.3 ± 0.1	1.3 ± 0.1
	4 wk	1.6 ± 0.3	1.7 ± 0.1	2.2 ± 0.2^*	2.1 ± 0.1^*
LDL (mg/dL)	1 wk	6.8 ±1.5	7.6 ± 0.6	7.5 ± 0.6	5.4 ± 0.9
	4 wk	10.2 ±2.8	15.3 ± 4.5^*	15.3 ± 2.6^*	20.2 ± 2.6^*,†

n=5 in each group.

WKY, Wistar Kyoto rat; SHR, spontaneous hypertensive rat; NC, normal cholesterol diet; HC, high cholesterol diet; LDL, low density lipoprotein; SBP, spontaneous hypertensive rat, WKY-NC, WKY-HC vs. SHR-NC, SHR-HC, p<0.01; Wall thickness, WKY-NC, WKY-HC vs. SHR-NC, SHR-HC, p<0.05; LDL, WKY-NC vs. WKY-HC, SHR-NC, p<0.05, WKY-NC, WKY-HC, SHR-NC vs. SHR-HC.

^* p<0.05,

^† p<0.01.

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