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Journal of Renin-Angiotensin-Aldosterone System
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Facilitative interaction between angiotensin II and oxidised LDL in cultured human coronary artery endothelial cells

Jawahar L Mehta

Departments of Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA, mehtajl@ uams.edu

Dayuan Li

Departments of Medicine and Physiology and Biophysics, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, USA

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.

Key Words: angiotensin II • oxidised-LDL • receptors • endothelial cells

Journal of Renin-Angiotensin-Aldosterone System, Vol. 2, No. 1 suppl, S70-S76 (2001)
DOI: 10.1177/14703203010020011201
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