Angiotensin II and atherosclerosis

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Abstract

Numerous clinical and laboratory data are now available supporting the hypothesis that the renin–angiotensin system is mechanistically relevant in the pathogenesis of atherosclerosis. The traditional role of the renin–angiotensin system in the context of blood pressure regulation has been modified to incorporate the concept that angiotensin II (Ang II) is a potent proinflammatory agent. In vascular cells, Ang II is a potent stimulus for the generation of reactive oxygen species. As a result, Ang II upregulates the expression of many redox-sensitive cytokines, chemokines, and growth factors that have been implicated in the pathogenesis of atherosclerosis. Extensive data now confirm that inhibition of the renin–angiotensin system inhibits atherosclerosis in animal models as well as in humans. These studies provide mechanistic insights into the precise role of Ang II in atherosclerosis and suggest that pharmacologic interventions involving the renin–angiotensin system may be of fundamental importance in the treatment and prevention of atherosclerosis.

Section snippets

Oxidative stress as a mechanistic link between angiotensin II and atherosclerosis

Perhaps the most intriguing aspect of the Ang II-mediated events in the arterial wall is the almost complete overlap with proposed mechanisms of atherogenesis. Many of the phenomena implicated in atherosclerosis can be reproduced by Ang II. Atherosclerosis is an inflammatory disease of vascular wall initiated and amplified by vascular oxidative stress.9 Ang II is also a very potent stimulus for both inflammation and oxidative stress.2 The important potential sources of oxidative stress in

Conclusion

In summary there is accumulating evidence from both clinical studies and laboratory investigations that the renin–angiotensin II system represents a critical, causal link in the pathogenesis of human atherosclerosis. The current studies provide mechanistic insights into the precise role of Ang II in atherosclerosis, which suggest that pharmacologic interventions involving the renin–angiotensin system may be of fundamental importance in the treatment and prevention of atherosclerosis.

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