Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins

Keidar, Shlomo; Kaplan, Marielle; Hoffman, Azik; Aviram, Michael

doi:10.1016/0021-9150(94)05514-j

Cited by 146 publications

(68 citation statements)

References 37 publications

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“…35 In contrast, administration of ACE inhibitors abolished macrophage recruitment in this experimental model, 36,37 and blockade of the AT 1 receptor by losartan was shown to prevent the accumulation of oxidative reactants, which abolished lipid peroxidation and the progression of atherosclerosis in an apolipoprotein E-deficient animal model. 38,39 The present study may have potential clinical implications by pointing to mechanisms by which ACE inhibitors reduce the incidence of reinfarctions, that is, the attenuation of proinflammatory processes in atherosclerotic plaques. If so, ACE inhibition should reduce serum markers of inflammation in patients treated with ACE inhibitors.…”

Section: Discussionmentioning

confidence: 79%

Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques

et al. 2000

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Background-Patients with an activated renin-angiotensin system (RAS) or genetic alterations of the RAS are at increased risk of myocardial infarction (MI). Administration of ACE inhibitors reduces the risk of MI, and acute coronary syndromes are associated with increased interleukin 6 (IL-6) serum levels. Accordingly, the present study evaluated the expression of angiotensin II (Ang II) in human coronary atherosclerotic plaques and its influence on IL-6 expression in patients with coronary artery disease. Methods and Results-Immunohistochemical colocalization of Ang II, ACE, Ang II type 1 (AT 1 ) receptor, and IL-6 was examined in coronary arteries from patients with ischemic or dilated cardiomyopathy undergoing heart transplantation (nϭ12), in atherectomy samples from patients with unstable angina (culprit lesion; nϭ8), and in ruptured coronary arteries from patients who died of MI (nϭ13). Synthesis and release of IL-6 was investigated in smooth muscle cells and macrophages after Ang II stimulation. Colocalization of ACE, Ang II, AT 1 receptor, and IL-6 with CD68-positive macrophages was observed at the shoulder region of coronary atherosclerotic plaques and in atherectomy tissue of patients with unstable angina. Ang II was identified in close proximity to the presumed rupture site of human coronary arteries in acute MI. Ang II induced synthesis and release of IL-6 shortly after stimulation in vitro in macrophages and rat smooth muscle cells. Conclusions-Ang II, AT 1 receptor, and ACE are expressed at strategic sites of human atherosclerotic coronary arteries, suggesting that Ang II is produced primarily by ACE within coronary plaques. The observation that Ang II induces IL-6 and their colocalization with the AT 1 receptor and ACE is consistent with the notion that the RAS may contribute to inflammatory processes within the vascular wall and to the development of acute coronary syndromes. (Circulation. 2000;101:1372-1378.)Key Words: interleukins Ⅲ angiotensin Ⅲ angina Ⅲ myocardial infarction Ⅲ arteries Ⅲ receptors R upture of atherosclerotic plaques occurs predominantly at the edges of the plaque's fibrous cap, the shoulder region, that is, areas of accumulated inflammatory cells, for example, macrophages, T-lymphocytes, and mast cells in close proximity to vascular smooth muscle cells (SMC). [1][2][3][4][5][6] The activated inflammatory cells stimulate their neighboring cells to erode the extracellular matrix through the release of inflammatory cytokines. The decay of the framework that forms the plaque cap leads to plaque rupture 1,7,8 and resembles the morphological correlate of an acute coronary syndrome. Serum levels of interleukin 6 (IL-6) are increased in patients with unstable angina 9 and may trigger the onset of an acute coronary syndrome. 10 IL-6 is known to be involved in the stimulation of matrix-degrading enzymes, for example, metalloproteinases. 11In parallel, the renin-angiotensin system (RAS) has been suggested to be involved in the development of acute coronary syndromes, based on the observat...

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Section: Discussionmentioning

confidence: 79%

Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques

et al. 2000

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“…26,27 An additional effect of ANGII is the upregulation of the lectin-like oxidized LDL receptor (LOX) -1 on endothelial cells and macrophages, an effect that may further enhance oxidized LDL infiltration in the vessel wall.The development of atherosclerosis occurs through structural changes of the vessel wall from migration and proliferation of smooth muscle cells up to plaque rupture. 28,29 Finally, ANGII inhibits the fibrinolytic system and enhances thrombosis by increased production of plasminogen activator inhibitor (PAI)-1, tissue factor (TF), and platelet activation and aggregation. 30,31,32,33 …”

Section: Furthermore Nf-b Activation By Angii Leads To Increased Expmentioning

confidence: 99%

Role of Ace Inhibitors In Atherosclerosis

Shafi

2013

Int J of Biomed & Adv Res

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“…95 Moreover, Ang IImediated macrophage lipid peroxidation was found to involve the action of cellular NADPH oxidase as well as 15-lipoxygenase. 96 It has been suggested that lipoxygenase and NADPH oxidase mediate the oxidative modification of LDL. 97 Thus, the antioxidative effect of ACEis seems to be mediated by decreasing the expression of the lipoxygenase enzyme.…”

Section: Ace Inhibitors As Antioxidantmentioning

confidence: 99%

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

2009

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Since their inception, angiotensin-converting enzyme (ACE) inhibitors have been used as first-line therapy for the treatment of cardiovascular and renal diseases. They restore the balance between the vasoconstrictive salt-retentive and hypertrophy-causing peptide angiotensin II (Ang II) and bradykinin, a vasodilatory and natriuretic peptide. As ACE is a promiscuous enzyme, ACE inhibitors alter the metabolism of a number of other vasoactive substances. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have been proven effective in the treatment of hypertension, and reduce mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction. They inhibit ischemic events and stabilize plaques. Furthermore, they delay the progression of diabetic nephropathy and neuropathy and act as antioxidants. Ongoing studies have elucidated protective roles for them in both memory-related disorders and cancer. INTRODUCTIONIn recent years, stressful and fiercely competitive lifestyles and food habits have compounded the problems of hypertension. Long-standing and stressful, progressively rising hypertension can lead to many disorders, including myocardial infarction (MI), cerebrovascular events, congestive heart failure, peripheral arterial insufficiency, premature mortality 1 and renal dysfunction leading to glomerulosclerosis and kidney artery aneurysm. 2 A number of therapies are available, but angiotensin-converting enzyme (ACE) inhibitors have been the preferred first-line therapy for hypertension, congestive heart failure, left ventricular (LV) systolic dysfunction and MI. 3,4 ACE inhibitors (ACEis) have been in use for the past two decades, and the interest in them is still growing. Recently, the discovery of domain-selective ACEis and new members of the renin-angiotensin system (RAS) (that is, angiotensin-converting enzyme 2) have again fueled the interest of researchers. Some new studies have expanded the already impressive clinical profile of ACEis. This review traces some already known and new facets of ACE inhibition and introduces new advances in the designing of a new generation of ACEis.

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Angiotensin II stimulates macrophage-mediated oxidation of low density lipoproteins

Cited by 146 publications

References 37 publications

Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques

Expression of Angiotensin II and Interleukin 6 in Human Coronary Atherosclerotic Plaques

Role of Ace Inhibitors In Atherosclerosis

Reinventing the ACE inhibitors: some old and new implications of ACE inhibition

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