Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree

Mauriello, Alessandro; Sangiorgi, Giuseppe; Fratoni, Stefano; Palmieri, Giampiero; Bonanno, Elena; Anemona, Lucia; Schwartz, Robert S.; Spagnoli, Luigi Giusto

doi:10.1016/j.jacc.2005.01.054

Cited by 206 publications

(130 citation statements)

References 33 publications

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“…88,91 They tend to cluster in the proximal segments of the major coronary arteries, where most plaque ruptures and thrombi are seen, 126 and rarely more than a few TCFAs exist simultaneously. 127,128 The absence of TCFAs in a patient indicates a low imminent risk for plaque rupture and thrombosis. An attempt to measure the risk conferred by their presence was done in the recent PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study.…”

Section: Thin Fibrous Capmentioning

confidence: 99%

Mechanisms of Plaque Formation and Rupture

Bentzon

Otsuka

Virmani

et al. 2014

Circulation Research

1,808

1,268

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Atherosclerosis causes clinical disease through luminal narrowing or by precipitating thrombi that obstructblood flow to the heart (coronary heart disease), brain (ischemic stroke), or lower extremities (peripheral vascular disease). The most common of these manifestations is coronary heart disease, including stable angina pectoris and the acute coronary syndromes. Atherosclerosis is a lipoprotein-driven disease that leads to plaque formation at specific sites of the arterial tree through intimal inflammation, necrosis, fibrosis, and calcification. After decades of indolent progression, such plaques may suddenly cause life-threatening coronary thrombosis presenting as an acute coronary syndrome. Most often, the culprit morphology is plaque rupture with exposure of highly thrombogenic, red cell-rich necrotic core material. The permissive structural requirement for this to occur is an extremely thin fibrous cap, and thus, ruptures occur mainly among lesions defined as thin-cap fibroatheromas. Also common are thrombi forming on lesions without rupture (plaque erosion), most often on pathological intimal thickening or fibroatheromas. However, the mechanisms involved in plaque erosion remain largely unknown, although coronary spasm is suspected. The calcified nodule has been suggested as a rare cause of coronary thrombosis in highly calcified and tortious arteries in older individuals. To characterize the severity and prognosis of plaques, several terms are used. Plaque burden denotes the extent of disease, whereas plaque activity is an ambiguous term, which may refer to one of several processes that characterize progression. Plaque vulnerability describes the short-term risk of precipitating symptomatic thrombosis. In this review, we discuss mechanisms of atherosclerotic plaque initiation and progression; how plaques suddenly precipitate life-threatening thrombi; and the concepts of plaque burden, activity, and vulnerability. (Circ Res.

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Section: Thin Fibrous Capmentioning

confidence: 99%

Mechanisms of Plaque Formation and Rupture

Bentzon

Otsuka

Virmani

et al. 2014

Circulation Research

1,808

1,268

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“…Macrophages play a key role in acute plaque destabilization and thrombus formation; they secrete proteases that digest the extracellular matrix and weaken the protective fibrous cap covering the atheromatous core and release in atherosclerotic plaques large amounts of tissue factor that accelerates thrombus formation after plaque rupture (5). Moreover, macrophage density measured by immunohistology was found to be higher in atherosclerotic plaques obtained from patients with recent acute coronary syndromes than in plaques obtained from patients with stable cardiovascular disease (6). Therefore, detection of high-risk plaques using noninvasive imaging could help to identify patients susceptible to plaque rupture and reduce the rate of acute coronary syndromes by early implementation of therapies aimed at plaque stabilization (7).…”

mentioning

confidence: 99%

Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with ¹⁸F-FDG PET/CT and Histology

Hyafil¹,

Cornily²,

Rudd³

et al. 2009

J Nucl Med

113

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Macrophages play a key role in atherosclerotic plaque rupture. The iodine-based contrast agent N1177 accumulates in macrophages, allowing for their detection with CT. In this study, we tested whether the intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlated with inflammatory activity evaluated with 18 F-FDG PET/CT and macrophage density on histology. Methods: Atherosclerotic plaques were induced in the aorta of New Zealand White rabbits (n 5 7) by a repeated balloon injury (4 wk apart) and 4 mo of hyperlipemic diet. Noninjured rabbits, fed a chow diet, were used as controls (n 5 3). A CT scan of the aorta (n 5 10) was acquired in each rabbit before, during, and at 2 h after intravenous injection of N1177 (250 mg of iodine/kg). One week later, the same rabbits underwent PET/CT 3 h after injection of 18 F-FDG (37 MBq/kg [1 mCi/kg]). CT enhancement was calculated as the difference in aortic wall densities between images obtained before and images obtained at 2 h after injection of N1177. Mean standardized uptake values were measured on PET axial slices of the aorta in regions of interest encompassing the vessel wall. Macrophage density was measured by immunohistology (anti-RAM-11 antibody) on corresponding aortic cross-sections. Results: N1177-enhanced CT measured stronger enhancement in the aortic wall of atherosclerotic rabbits than in control rabbits (10.0 6 5.2 vs. 2.0 6 2.1 Hounsfield units, respectively; P , 0.05). After the injection of 18 F-FDG, PET detected higher standardized uptake values in the aortic wall of atherosclerotic rabbits than in control rabbits (0.61 6 0.12 vs. 0.21 6 0.02; P , 0.05). The intensity of enhancement in the aortic wall measured with CT after injection of N1177 correlated with 18 F-FDG uptake on PET/CT (r 5 0.61, P , 0.001) and macrophage density on immunohistology (r 5 0.63, P , 0.001). Conclusion: The intensity of enhancement detected with CT in the aortic wall of rabbits injected with N1177 correlates with intense uptake of 18 F-FDG measured with PET and with macrophage density on histology, suggesting a role for N1177 in noninvasive identification of high-risk atherosclerotic plaques with CT.

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“…5 The balance between inflammatory and anti-inflammatory activity controls the progression of atherosclerosis, and both vulnerable and stable coronary plaques of patients dying of acute MI are diffusely infiltrated by inflammatory cells. 6 Inflammation plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. 7 Even though the reduction of inflammation, reflected by C-reactive protein (CRP) levels, through statin therapy improve the clinical outcome, 8,9 the fact that CRP contributes to the statistical risk of CAD makes it unlikely that it actually causes MI.…”

mentioning

confidence: 99%

Patients With Low High-Density Lipoprotein-Cholesterol or Smoking are More Likely to Develop Myocardial Infarction Among Subjects With a Visible Lesion or Stenosis in Coronary Artery

Sun

Yang

Pei

et al. 2006

Circ J

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Background Traditional contrast coronary arteriography affords only an indirect view of aspects of atheromata related to their propensity to trigger thromboses, so it is urgent to recognize the vulnerable person who is more likely to develop myocardial infarction (MI) among patients with visible lesion or stenosis in coronary artery. Methods and ResultsTwo hundred and eighty-eight patients (144 MI patients, 144 controls) who had either a visible lesion or differing extent of stenosis in 1 or more major coronary arteries were consecutively enrolled. Lipid profile, C-reactive protein (CRP), smoking, hypertension, dyslipidemia and diabetes were analyzed for their association with MI. No differences in the prevalence of dyslipidemia, hypertension or diabetes was found between the patients with MI and those without, and CRP, triglycerides, total cholesterol and low-density lipoprotein-cholesterol levels did not differ between the 2 groups (all p>0.05). However, high-density lipoproteincholesterol (HDL-C) was significantly lower in the patients with MI than in those without (1.06±0.30 vs 1.14±0.32 mmol/L, p=0.024). On multivariate analysis after adjustment for age and gender, adjusted odds ratio (95% confidence interval) of MI was 0.44 (0.20-0.96) for HDL-C, p=0.038; 2.6 (1.48-4.56, p=0.001) for smoking, which indicated that high HDL-C was protective for MI, and smoking was associated with an increased risk of MI. Conclusions The present findings indicate that among subjects with a visible lesion or stenosis in coronary arteries, those with low HDL-C or smokers are more likely to develop MI. (Circ J 2006; 70: 1602 -1605

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Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree

Abstract: This histopathologic study found that both vulnerable and stable coronary plaques of patients dying of AMI are diffusely infiltrated by inflammatory cells.

Cited by 206 publications

References 33 publications

Mechanisms of Plaque Formation and Rupture

Mechanisms of Plaque Formation and Rupture

Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with ¹⁸F-FDG PET/CT and Histology

Patients With Low High-Density Lipoprotein-Cholesterol or Smoking are More Likely to Develop Myocardial Infarction Among Subjects With a Visible Lesion or Stenosis in Coronary Artery

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Diffuse and Active Inflammation Occurs in Both Vulnerable and Stable Plaques of the Entire Coronary Tree

Abstract: This histopathologic study found that both vulnerable and stable coronary plaques of patients dying of AMI are diffusely infiltrated by inflammatory cells.

Cited by 206 publications

References 33 publications

Mechanisms of Plaque Formation and Rupture

Mechanisms of Plaque Formation and Rupture

Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with 18F-FDG PET/CT and Histology

Patients With Low High-Density Lipoprotein-Cholesterol or Smoking are More Likely to Develop Myocardial Infarction Among Subjects With a Visible Lesion or Stenosis in Coronary Artery

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Quantification of Inflammation Within Rabbit Atherosclerotic Plaques Using the Macrophage-Specific CT Contrast Agent N1177: A Comparison with ¹⁸F-FDG PET/CT and Histology