Angiotensin II Type 2 Receptor–Mediated Gene Expression Profiling in Human Coronary Artery Endothelial Cells

Background Several studies have shown that angiotensin II (Ang II) and oxidised low-density lipoprotein (ox-LDL) are critical factors in atherosclerosis. In this study, we examined the molecular basis of mutually facilitative interactions between Ang II and ox-LDL in human coronary artery endothelial cells (HCAECs). Methods and results We observed that incubation of cultured HCAECs with Ang II (10-12 to 10-6 M) for 24 hours caused a concentration-dependent increase in the expression of mRNA and protein of a specialised receptor for ox-LDL (LOX-1). These effects of Ang II were completely blocked by pretreatment of HCAECs with candesartan (10-6 M), a specific AT1-receptor blocker, but not by PD 123319 (10-6 M), a specific AT2-receptor blocker. On the other hand, incubation of HCAECs with ox-LDL (10 and 40 µg/ml) for 24 hours progressively upregulated AT1-, but not AT 2-, receptor mRNA and protein. Pretreatment of cells with the anti-oxidant alpha-tocopherol (1—5 x 10-6 M) inhibited the upregulation of AT1-receptor expression induced by ox-LDL (p<0.05). To determine the significance of expression of AT1-receptors and LOX-1, we measured cell injury in response to Ang II and ox-LDL. Incubation of cells with both ox-LDL and Ang II synergistically increased cell injury, measured as cell viability and LDH release, compared with either ox-LDL or Ang II alone (both p<0.05). Alpha-tocopherol, as well as candesartan, attenuated cell injury in response to Ang II and ox-LDL (both p<0.05). Conclusions These observations show that Ang II upregulates a novel endothelial receptor for ox-LDL (LOX-1) gene expression and ox-LDL in turn upregulates Ang II AT 1receptor gene expression. This interaction between Ang II and ox-LDL further augments cell injury in HCAECs. These findings provide basis for the use of AT1-receptor blockers and anti-oxidants in designing therapy for atherosclerosis and myocardial ischaemia.

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Angiotensin II via Activation of Type 1 Receptor Upregulates Expression of Endoglin in Human Coronary Artery Endothelial Cells

Hypertension ◽

10.1161/hy1101.092971 ◽

2001 ◽

Vol 38 (5) ◽

pp. 1062-1067 ◽

Cited By ~ 15

Author(s):

Dayuan Li ◽

Hongjiang Chen ◽

Jawahar L. Mehta

Keyword(s):

Endothelial Cells ◽

Coronary Artery ◽

Angiotensin Ii ◽

Human Coronary Artery

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Time Series Gene Expression Profiling and Temporal Regulatory Pathway Analysis of Angiotensin II Induced Atrial Fibrillation in Mice

Frontiers in Physiology ◽

10.3389/fphys.2019.00597 ◽

2019 ◽

Vol 10 ◽

Cited By ~ 5

Author(s):

Yu-Xuan Wu ◽

Xiao Han ◽

Chen Chen ◽

Lei-Xin Zou ◽

Zhi-Chao Dong ◽

...

Keyword(s):

Gene Expression ◽

Atrial Fibrillation ◽

Time Series ◽

Angiotensin Ii ◽

Gene Expression Profiling ◽

Pathway Analysis ◽

Expression Profiling ◽

Regulatory Pathway ◽

Time Series Gene Expression

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Gene expression profiling of human umbilical vein endothelial cells exposed to myricetin

BioChip Journal ◽

10.1007/s13206-013-7404-4 ◽

2013 ◽

Vol 7 (4) ◽

pp. 335-343 ◽

Cited By ~ 1

Author(s):

Seung Eun Lee ◽

Yong Seek Park

Keyword(s):

Gene Expression ◽

Endothelial Cells ◽

Gene Expression Profiling ◽

Expression Profiling ◽

Umbilical Vein ◽

Human Umbilical Vein ◽

Umbilical Vein Endothelial Cells

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Gene expression profiling in whole blood of patients with coronary artery disease

Clinical Science ◽

10.1042/cs20100043 ◽

2010 ◽

Vol 119 (8) ◽

pp. 335-343 ◽

Cited By ~ 86

Author(s):

Chiara Taurino ◽

William H. Miller ◽

Martin W. McBride ◽

John D. McClure ◽

Raya Khanin ◽

...

Keyword(s):

Gene Expression ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Gene Expression Profiling ◽

Whole Blood ◽

Expression Profiling ◽

Gene Expression Analysis ◽

Differentially Expressed ◽

Differentially Expressed Mirnas ◽

Artery Disease

Owing to the dynamic nature of the transcriptome, gene expression profiling is a promising tool for discovery of disease-related genes and biological pathways. In the present study, we examined gene expression in whole blood of 12 patients with CAD (coronary artery disease) and 12 healthy control subjects. Furthermore, ten patients with CAD underwent whole-blood gene expression analysis before and after the completion of a cardiac rehabilitation programme following surgical coronary revascularization. mRNA and miRNA (microRNA) were isolated for expression profiling. Gene expression analysis identified 365 differentially expressed genes in patients with CAD compared with healthy controls (175 up- and 190 down-regulated in CAD), and 645 in CAD rehabilitation patients (196 up- and 449 down-regulated post-rehabilitation). Biological pathway analysis identified a number of canonical pathways, including oxidative phosphorylation and mitochondrial function, as being significantly and consistently modulated across the groups. Analysis of miRNA expression revealed a number of differentially expressed miRNAs, including hsa-miR-140-3p (control compared with CAD, P=0.017), hsa-miR-182 (control compared with CAD, P=0.093), hsa-miR-92a and hsa-miR-92b (post- compared with pre-exercise, P<0.01). Global analysis of predicted miRNA targets found significantly reduced expression of genes with target regions compared with those without: hsa-miR-140-3p (P=0.002), hsa-miR-182 (P=0.001), hsa-miR-92a and hsa-miR-92b (P=2.2×10−16). In conclusion, using whole blood as a ‘surrogate tissue’ in patients with CAD, we have identified differentially expressed miRNAs, differentially regulated genes and modulated pathways which warrant further investigation in the setting of cardiovascular function. This approach may represent a novel non-invasive strategy to unravel potentially modifiable pathways and possible therapeutic targets in cardiovascular disease.

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