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. 1990 Jul;137(1):7–12.

Influence of the angiotensin system on endothelial and smooth muscle cell migration.

L Bell 1, J A Madri 1
PMCID: PMC1877705  PMID: 2164777

Abstract

The blood vessel wall's response to injury is an important determinant of luminal size and vessel function. The physiologic migration of endothelial cells from the edges of a wound and the pathophysiologic migration of medial smooth muscle cells into the intima are two important components of the vessel wall's response to injury. The influence of the angiotensin system on endothelial and smooth muscle cell migration have not been examined. In the present study, the influence of angiotensin system components on bovine aortic endothelial cell (BAEC) and bovine aortic smooth muscle cell (BASMC) migration after release of cultured cell monolayers from contact inhibition was determined. The angiotensin-converting enzyme (ACE) inhibitor lisinopril increased BAEC migration 41% +/- 3% (P less than 0.001), as did the specific angiotensin II antagonist sar1, ile8-angiotensin II (SAR) (41% +/- 3% (P less than 0.001). Exogenous angiotensin I and angiotensin II did not affect BAEC migration. Exogenous angiotensin II abolished the effect of lisinopril on BAEC migration. Lisinopril increased cell-associated u-plasminogen activator (u-PA) 23% +/- 3% (P less than 0.001) in migrating BAEC and angiotensin II abolished this increase. SAR increased u-PA 33% +/- 0% (P less than 0.001). In contrast, these agents had the opposite effect on smooth muscle cells. Angiotensin II increased smooth muscle cell migration 40% +/- 3% (P less than 0.001), and this effect was abolished by SAR. Angiotensin II also increased cell-associated u-PA 83% +/- 7% (P less than 0.001) in migrating BASMC. The increase in BAEC migration with inhibition of endothelial cell angiotensin II stimulation, either with lisinopril or SAR, also was associated with an increase in cell-associated u-PA. These results indicate that lisinopril interrupts an autocrine pathway in endothelial cells, in which endothelial cell-derived angiotensin I is converted to angiotensin II by ACE, and imply that angiotensin-converting enzyme inhibitors in vivo would act to reduce vessel wall injury by directly increasing the rate of endothelial cell wound closure; by increasing the antithrombotic tendency of the endothelium via enhanced u-PA; and indirectly, by decreasing production of angiotensin II and thereby the rate of smooth muscle cell migration into the intima.

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Selected References

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