Effects of Angiotensin II and Shear Stress Interaction on Vascular Inflammation

Sung Hyun Choi; Eun Hye Park; Yujin Oh; Sang Hong Baek

doi:10.5646/jksh.2011.17.1.17

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Choi, Park, Oh, and Baek: Effects of Angiotensin II and Shear Stress Interaction on Vascular Inflammation

Original Article

J Korean Soc Hypertens 2011;17(1):17-27.

Published online: 10 March 2011

DOI: https://doi.org/10.5646/jksh.2011.17.1.17

Effects of Angiotensin II and Shear Stress Interaction on Vascular Inflammation

Sung Hyun Choi, MS¹, Eun Hye Park, MS¹, Yujin Oh, BSc³, Sang Hong Baek, MD^1,^2,

¹Laboratory of Cardiovascular Research, The Catholic University of Korea School of Medicine, Seoul, Korea

²Division of Cardiovascular Medicine, St. Seoul Mary’s Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea

³Department Biology, University of Miami College of Arts and Sciences, Coral Gables, FL, USA

Tel: 02) 2258-6030, Fax: 02) 591-1506 E-mail: whitesh@catholic.ac.kr

Received 20 December 201031 December 2010 Accepted 3 January 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:

Angiotensin II (AngII) and abnormal oscillatory shear stress are highly associated with vascular inflammation including atherosclerosis. However, it is poorly understood how interactions between AngII and shear stress in human aortic endothelial cells (HAEC) are involved in mechanisms by which cellular adhesion molecules are expressed. The purpose of this study was to improve that understanding.

Methods:

AngII (10^-7M for 6 hr) and two-types of shear stress treatments were used: laminar shear stress (LS: unidirectional, 12 dynes/cm²) and oscillatory shear stress (OS: bi-directional, 5 dynes/cm², 1 Hz) in HAEC. Immunoblotting was used to detect expression of cellular adhesion molecules markers such as vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1).

Results:

AngII significantly increased VCAM1 and ICAM1 expression in HAEC that had been reduced due to pretreatment with telmisartan. AngII-LS co-stimulation and AngII-OS co-stimulation significantly increased VCAM1 and ICAM1 expression in HAEC. The expression levels of VCAM1 and ICAM1 were also, significantly reduced when pretreated with telmisartan. However, VCAM1 and ICAM1 expression were significantly reduced under LS and OS stimulation.

Conclusions:

Telmisartan may modulate the expressions of VCAM1 and ICAM1 via different types of shear stress in HAEC that are activated by AngII.

Keywords: Vascular cell adhesion molecule 1, Intercellular adhesion molecule 1, Angiotensin II, Shear stress, Human aortic endothelial cell

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Fig. 1.

MTS (HAEC viability) assay. HAEC viability was significantly decreased in 10^-6M AngII treated group as compared to the control. OD (optical density) ratio. AngII was incubated for 18 hours with EBM-2. *p<0.01 compared to the control. Data were obtained in at least 3 independent experiments, obtained with different sets of cells. MTS, 3-(4,5-demethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-Sulfopheynyl)-2H-tetrazolium; HAEC, human aortic endothelial cells.

Fig. 2.

Analysis of VCAM1 expression according to different concentrations of AngII. The expression of VCAM1 was measured by western blot (A), and quantitative results that normalized with actin are shown (B). AngII was incubated for 18 hours with EBM-2. Data were obtained in at least 3 independent experiments, obtained with different sets of cells. VCAM1, vascular cell adhesion molecule 1; AngII, angiotensin II.

Fig. 3.

Analysis of the VCAM1 expression according to different exposure durations of Ang II. The expression of VCAM1 was measured by western blot (A) and quantitative results that normalized by actin are shown (B). AngII treated concentration was 10^-7M cotreated with EBM-2. Data were obtained in at least 3 independent experiments, obtained with different sets of cells. VCAM1, vascular cell adhesion molecule 1; AngII, angiotensin II.

Fig. 4.

Analysis of the VCAM1 and ICAM1 expression after AngII with and without pre-treatment of ARB (telmisartan). The expression of VCAM1 and ICAM1 was analyzed by western blot (A), and quantitative results that normalized by actin are shown (B, C). VCAM1 and ICAM1 expressions were increased by treatment with AngII as compared to the control, and their expression was significantly reduced after pre-treatment of ARB. The degree of reduction in ICAM1 was larger than VCAM1. AngII: 10^-7M, for 18 hours in EBM-2, ARB: telmisartan, 10^-7M, for 30 minutes before treatment with AngII in EBM-2. Data were obtained in at least 3 independent experiments, obtained with different sets of cells. VCAM1, vascular cell adhesion molecule 1; AngII, angiotensin II.

Fig. 5.

Representative HAEC morphology after laminar shear stress and oscillatory shear stress. Cell morphologyunder light microscopy of the control group (A), treatment with unidirectional laminar shear stress (12 dynes/cm²) in HAEC (B), and treatment with bidirectional oscillatory shear stress (5 dynes/cm², 1 Hz) in HAEC (C). Shear stresses were treated for 18 to 19 hours. HAEC, human aortic endothelial cells.

Fig. 6.

Analysis of VCAM1 and ICAM1 expressions by interaction between laminar shear stress (LS) and Ang II. The expression levels of VCAM1 and ICAM1 were detected by western blot (A), and quantitative result that normalized by actin are shown (B). LS or LS and AngII costimulation increased VCAM1 and ICAM1 expression levels as compared to the control. VCAM1 expression was significantly reduced by pre-treatment of ARB. LS (force: 12 dynes/cm², incubation times: 18 hr), AngII (concentration: 10^-7M, incubation times: 6hr), ARB (telmisartan, concentration: 10^-7M, incubation times: 30 min). *p<0.01, compared to control, **p<0.05, compared to control, † p< 0.01, compared to LS group. Data were obtainedin at least 3 independent experiments, obtained with different sets of cells. VCAM1, vascular cell adhesion molecule 1; ICAM1, intercellular adhesion molecule 1; AngII, angiotensin II.

Fig. 7.

Analysis of VCAM1 and ICAM1 expressions by interaction between oscillatory shear stress (OS) and Ang II. The expression levels of VCAM1 and ICAM1 were detected by western blot (A) and quantitative result that normalized by actin are shown (B) OS or OS and AngII costimulation increased VCAM1 and ICAM1 expression levels as compared to the control. ICAM1 expression was significantly reduced by pre-treatment of ARB. LS (force: 12 dynes/cm², incubation times: 18 hr), AngII (concentration: 10^-7M, incubation times: 6hr), ARB (telmisartan, concentration: 10^-7M, incubation times: 30 min). *p<0.01, compared to control, **p<0.05, compared to control, †p<0.01, compared to LS group. VCAM1, vascular cell adhesion molecule 1; ICAM1, intercellular adhesion molecule 1; LS, laminar shear stress.

Table 1.

The expression levels of VCAM1 and ICAM1 in LS and OS treatment groups as compared to control group

	Compared with Control Group (%)
	LS				OS
	-	Ang II	TERT	TERT+Ang II	-	Ang II	TERT	TERT+Ang II
VCAM1	+168.5	+126.2	NS	NS	+132.1	+67.9	+153.2	+178.8
ICAM1	+51.1	+207.8	+221.8	+361.6	+620.1	+537.9	+753.6	+352.5

LS, lanimar shear stress; OS, oscillatory shear stress; Ang II, angiotensin II; TERT, telmisartan; NS, not significant. VCAM, vascular cell adhesion molecule 1; ICAM1, intercellular adhesion molecule 1.

Table 2.

The expression levels of VCAM1 and ICAM1 in LS and OS treatment groups as compared to each groups control (LS only and OS only)

	Compared with control group (%)
	LS			OS
	Ang II	TERT	TERT+Ang II	Ang II	TERT	TERT+Ang II
VCAM1	NS	-56.6	-60.4	-27.7	NS	NS
ICAM1	+103.7	+112.9	+205.5	NS	NS	-37.1

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