Angiotensin II as a Mediator of Inflammation in Atherosclerosis

Phillips, M. Ian; Kagiyama, Shuntaro; Chen, Hongjiang; Mehta, J. L.

doi:10.1007/978-3-0348-8239-2_8

Cited by 88 publications

(106 citation statements)

References 33 publications

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“…56 Activation of NF-B by the AT 1 receptor induces redox-sensitive genes for certain endothelial CAMs (eg, VCAM-1), cytokines (eg, tumor necrosis factor [TNF]-␣), and chemokines (monocyte chemoattractant protein-1). 57 Ang II can also engage the AT 1 receptors on leukocytes to promote ␤ 2 -integrin upregulation. 47 Superfusion of the rat mesentery with subvasoconstrictor doses of Ang II induces an AT 1 receptor-dependent rolling, firm adhesion and emigration of leukocytes, and an enhanced production of ROS in postcapillary venules.…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Modulation of the Inflammatory Response in Cardiovascular Disease

2004

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Abstract-There is a growing body of evidence that inflammation might play an important role in the initiation and progression of cardiovascular diseases (CVDs). The designation of CVD as a chronic inflammatory process is further supported by evidence that the risk factors for CVD cause endothelial cells throughout the vascular tree to assume an inflammatory phenotype. These activated endothelial cells characteristically exhibit oxidative stress and increased adhesiveness for circulating leukocytes. Although initial efforts to define the mechanisms underlying the inflammatory phenotype in diseased endothelial cells have focused on the linkage between oxidative stress and adhesion molecule activation/expression, recent work has implicated a variety of additional factors that can modulate the magnitude and/or nature of the inflammatory responses in CVD. Platelets, angiotensin II, and the CD40/CD40 ligand signaling system are gaining recognition as contributors to the pathogenesis of CVD. These factors appear to converge with known pathways that link oxidative stress with adhesion molecule expression and help to explain the apparent integration of coagulation with inflammation in CVD. These factors also hold the promise of offering multiple sites for therapeutic intervention in CVD. Key Words: oxidative stress Ⅲ integrins Ⅲ angiotensin II Ⅲ adhesion molecules I nflammation is gaining widespread attention for its role in the initiation and progression of cardiovascular disease (CVD). Epidemiological studies have revealed strong associations between biochemical markers of systemic inflammation and both the presence of and future risk for symptomatic CVD. Animal experimentation as well as clinical studies has provided convincing evidence that the known risk factors for CVD (hypertension, diabetes, hypercholesterolemia, and smoking) can elicit both an inflammatory and a prothrombogenic phenotype in the vascular system. The phenotypic changes are more pronounced in endothelial cells and can include oxidative stress, increased expression of endothelial cell adhesion molecules (CAMs), activation of cell signaling pathways (eg, the CD40/CD40 ligand [CD40L] dyad), and the consequent adhesion and activation of leukocytes and platelets. In the microcirculation, the inflammatory manifestations of CVD are more readily visible in postcapillary venules. There is growing evidence, however, that the endothelium-dependent arteriolar dysfunction often associated with CVD is also linked to the systemic inflammatory response. [1][2][3][4] Because the expression of adhesion glycoproteins by activated endothelial cells is a rate-determining step in the recruitment of inflammatory cells, much attention has been devoted to the role of endothelial CAMs in CVD. This attention has produced considerable evidence for the: (1) altered endothelial CAM expression in animal models of CVD 2,5 ; (2) use of circulating levels of soluble endothelial CAMs (eg, soluble intercellular adhesion molecule-1 [sICAM-1]) as a marker for the severity of inflammati...

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Section: Renin-angiotensin Systemmentioning

confidence: 99%

Modulation of the Inflammatory Response in Cardiovascular Disease

2004

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“…6 These tissue-derived sources of ACE have been shown to upregulate the inflammatory response. [7][8][9] Additionally, T and B lymphocytes, macrophages and neutrophils express angiotensin type 1 receptors. 7,10,11 Consistent with a role for ACE in inflammatory processes, ACE inhibitors suppress cytokine production in stimulated mononuclear cells.…”

Section: Introductionmentioning

confidence: 99%

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Does Not Alter Sepsis Outcome in Ventilated Very Low Birth Weight infants

2004

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OBJECTIVE:This study compared the effect of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the incidence and outcome of sepsis in ventilated very low birth weight infants. STUDY DESIGN:Infectious complications were retrospectively determined in 295 (234 African-American, 58 Caucasian and three Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 g at birth) and compared ACE I/D genotype. RESULTS:The incidence of the D allele in the study population was 0.60. A total of 113 (38.3%) infants were homozygous DD, 128 (43.4%) were heterozygous ID and 54 (18.3%) were homozygous II. One or more episodes of late BSI developed in 28 (52%) of 54 infants with the II genotype, 66 (52%) of 128 infants with the ID genotype and 52 (46%) of 113 infants with the DD genotype (p ¼ 0.618). Neither the rates of non-CONS BSI (II: 24%, ID: 23%, DD: 22%; p ¼ 0.937) nor multiple bacteremic/fungemic episodes (II: 13%, ID: 16%, DD: 12%; p ¼ 0.641) were different between genotype groups. The ACE I/D polymorphism had no effect on sepsis-related mortality (II: 7%, ID: 5%, DD: 4%; p ¼ 0.692). Sepsis mortality for infants with late BSI was 14% in infants with the II genotype, 9% with the ID genotype and 10% with the DD genotype (p ¼ 0.764). CONCLUSIONS:The ACE I/D polymorphism does not have a significant effect on the incidence or outcome of sepsis in ventilated VLBW infants.

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“…However, it is becoming increasingly apparent that Ang II also possesses potent proinflammatory properties, such as enhancing reactive oxygen species (ROS) generation, 1 increasing the expression of cell adhesion molecules (CAMs) and stimulating the release of cytokines and chemoattractants such as interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. [2][3][4] Ang II stimulates superoxide release from NAD(P)H oxidase by engaging the high-affinity Ang II type-1 receptor (AT1-R), thereby initiating the phosphorylation of critical enzyme subunits. 5,6 In vitro, Ang II elevates surface expression of CAMs 7 such as vascular CAM-1 (VCAM-1), 8 intercellular adhesion molecule-1 (ICAM-1), 9 and E-selectin.…”

mentioning

confidence: 99%

Angiotensin II Type-1 Receptor Antagonism Attenuates the Inflammatory and Thrombogenic Responses to Hypercholesterolemia in Venules

et al. 2005

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Abstract-Hypercholesterolemia elicits an inflammatory response in the microvasculature that is accompanied by an increased expression of angiotensin II type-1 receptors (AT1-R) on platelets, leukocytes, and endothelial cells. AT1-R blockade attenuates inflammatory responses to angiotensin II (eg, adhesion molecule expression and reactive oxygen species production). We investigated whether AT1-R antagonism attenuates the platelet and leukocyte recruitment induced by acute hypercholesterolemia in postcapillary venules. Leukocyte and platelet adhesion and oxidative stress were quantified by intravital microscopy in cremaster muscle, and P-selectin and AT1-R expression was determined in mice placed on a normal diet (ND) or high-cholesterol diet (HCD) for 2 weeks. Platelet and leukocyte adhesion was significantly elevated by hypercholesterolemia. In HCD mice receiving losartan (HCD-Los) in drinking water, platelet and leukocyte recruitment was reduced to ND levels. Increased platelet adhesion was observed in HCD mice receiving platelets from HCD-Los mice, consistent with a direct beneficial action of losartan on the vessel wall. Hypercholesterolemia elicited an oxidative stress in venules and an increased expression of P-selectin and AT1-R. The oxidative stress and AT1-R upregulation were reduced by losartan, but the P-selectin response was not. We propose that AT1-R engagement contributes to the prothrombogenic and proinflammatory state induced in venules by hypercholesterolemia. Key Words: receptors, angiotensin II Ⅲ microcirculation Ⅲ hypercholesterolemia Ⅲ leukocytes I t is well established that angiotensin II (Ang II), the effector component of the renin-angiotensin system, is a potent vasoconstrictor that plays a key role in the maintenance of blood pressure and fluid homeostasis. However, it is becoming increasingly apparent that Ang II also possesses potent proinflammatory properties, such as enhancing reactive oxygen species (ROS) generation, 1 increasing the expression of cell adhesion molecules (CAMs) and stimulating the release of cytokines and chemoattractants such as interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1. 2-4 Ang II stimulates superoxide release from NAD(P)H oxidase by engaging the high-affinity Ang II type-1 receptor (AT1-R), thereby initiating the phosphorylation of critical enzyme subunits. 5,6 In vitro, Ang II elevates surface expression of CAMs 7 such as vascular CAM-1 (VCAM-1), 8 intercellular adhesion molecule-1 (ICAM-1), 9 and E-selectin. 10 In vivo, superfusion of postcapillary venules with Ang II results in leukocyte recruitment and ROS generation. 11,12 These leukocyte adhesion responses appear to be mediated by a ROSdependent mobilization of preformed P-selectin to the endothelial surface. 11,12 Ang II can act as an immunomodulatory agent that engages the AT1-R to increase the number of Th1 cytokine (interferon-␥)-producing T cells 13 and elevate CD40 expression on circulating monocytes. 14 Ang II may also exert some of its proinflammatory effects through activatio...

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Angiotensin II as a Mediator of Inflammation in Atherosclerosis

Cited by 88 publications

References 33 publications

Modulation of the Inflammatory Response in Cardiovascular Disease

Modulation of the Inflammatory Response in Cardiovascular Disease

Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Does Not Alter Sepsis Outcome in Ventilated Very Low Birth Weight infants

Angiotensin II Type-1 Receptor Antagonism Attenuates the Inflammatory and Thrombogenic Responses to Hypercholesterolemia in Venules

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