Novel mechanisms linking angiotensin II and early atherogenesis.

We propose that Ang II exerts an as yet uncharacterized immunomodulatory effect on monocyte maturation, differentiation, or extravasation, which may depend on the myelomonocytic phenotype. Since the myelopoietic process originating at stem cells and culminating in release to the blood is at least 6 days, it is conceivable that the observation of reduced monocyte CD11b expression two weeks after completion of losartan treatment indicates a suppression of the CD11b phenotype in newly released CD14(+)/CD45(+) monocytes. Other studies employing suppression of AT(1)-receptors with deoxy-oligonucleotides have reported effects on blood pressure that surpass those predicted by the duration of the treatment.(87) These data would suggest that it is possible to interrupt a stimulatory signal by Ang II through a gene-related mechanism that in our experiments may reside in the mechanisms that regulate myelopoiesis. While our knowledge of the role of Ang II in the regulation of monocyte formation and function is incomplete, we have taken a first step in attempting to synthesize the data described above into a comprehensive hypothesis for further evaluation of the factors that initiate atherogenesis. Such effects may crucially contribute to the clinical benefit of AT(1)-receptor antagonists, independent of depressor effects, and may represent a paradigm for novel, anti-inflammatory actions by this class of drugs.