Angiotensin II and vascular inflammation.
Vascular inflammation is involved in the initiation and progression of atherosclerosis, and is also present in hypertension- and diabetes-induced vascular complications. Angiotensin II (Ang II), the key effector of the renin-angiotensin system (RAS), plays a central role in the regulation of blood pressure and electrolyte homeostasis. There is accumulating evidence to indicate that Ang II is also capable of inducing inflammatory response in the vascular wall. This review summarizes the current understanding of the molecular mechanisms and signal transduction pathways of Ang II-induced vascular inflammation. The roles of modulators of Ang II-induced inflammatory response, such as nitric oxide (NO), bradykinin, cyclooxygenase-2 (COX-2), endothelin-1 (ET-1), and epoxyeicosatrienoic acids (EETs), are also discussed. The current data suggest that Ang II modifies several steps of inflammatory response, such as increase of vascular permeability, leukocyte infiltration, tissue hypertrophy/proliferation, and fibrosis. Ang II, via the type 1 (AT1) receptors, enhances the production of reactive oxygen species (ROS) through stimulation of NAD(P)H oxidase in the vascular wall. Increased oxidative stress contributes to endothelial dysfunction and to vascular inflammation by stimulating the redox-sensitive transcription factors (NF-kappaB) and by upregulating adhesion molecules, cytokines, and chemokines. The pro-inflammatory action of Ang II may help us to understand the molecular mechanisms of hypertension- and diabetes-induced vascular complication as well as the pleiotropic actions of drugs interfering with RAS.
Cheng
Zhong Jian
ZJ
Institute of Biomedicine, Pharmacology, University of Helsinki, Finland.
Vapaatalo
Heikki
H
Mervaala
Eero
E
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001808:Blood Vessels / Q000503:physiopathology*; D002199:Capillary Permeability; D051546:Cyclooxygenase 2; D019332:Endothelin-1 / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000503:physiopathology*; D008565:Membrane Proteins; D009569:Nitric Oxide / Q000502:physiology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D015398:Signal Transduction
D019332:Endothelin-1; D008565:Membrane Proteins; D000804:Angiotensin II; D009569:Nitric Oxide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases