Plaque rupture and/or erosion are considered the leading cause of cardiovascular events. To elucidate this process, we demonstrated that during cholesterol crystallization the occupied volume increases rapidly and sharp-tipped crystals cut through thin biological membranes in their path. The amount of cholesterol correlated directly with both peak level and rate of crystal growth (r = 0.98; r = 0.99; p < 0.01, respectively). These observations suggest that crystallization of cholesterol in atherosclerotic plaques can induce cap rupture and/or erosion. Observations by scanning electron microscopy confirmed similar findings of cholesterol crystals perforating the lumen surface in human coronary artery segments with ruptured plaque.
SummaryBackground: Plaque rupture and/or erosion is the leading cause of cardiovascular events; however, the process is not well understood. Although certain morphologic characteristics have been associated with ruptured plaques, these observations are of static histological images and not of the dynamics of plaque rupture. To elucidate the process of plaque rupture, we investigated the transformation of cholesterol from liquid to solid crystal to determine whether growing crystals are capable of injuring the plaque cap.Hypothesis: We hypothesized that during cholesterol crystallization the spatial configuration rapidly changes, causing forceful expansion of sharp-edged crystals that can damage the plaque cap.Methods: Two experiments were performed in vitro: first, cholesterol powder was melted in graduated cylinders and allowed to crystallize at room temperature. Volume changes from liquid to solid state were measured and timed. Second, thin biological membranes (20-40 µm) were put in the path of growing crystals to determine damage during crystallization.Results: As cholesterol crystallized, the peak volume increased rapidly by up to 45% over 3 min and sharp-tipped
Background-It has been shown that plaque uptake of fluorodeoxyglucose is proportional to macrophage density. We tested the hypothesis that arterial thrombosis occurs in areas with high fluorodeoxyglucose uptake and that computed tomography angiography (CTA) can detect thrombi in vessels. Methods and Results-Twenty New Zealand White rabbits were studied before and after atherosclerosis induction through de-endothelialization and a high-cholesterol diet; 14 were then thrombus triggered. CTA/positron emission tomography scans were performed before cholesterol diet, at the middle diet feeding, at the end of diet feeding, and after triggering. Serum inflammatory markers were measured. Maximal standardized uptake value was measured over the thoracic and upper and lower abdominal aortas and correlated with thrombosis and macrophage density on sections from the same sites. Aortic diameters averaged 2.84Ϯ1.16 mm. The sensitivity, specificity, and accuracy of CTA for detecting thrombi were 92%, 89%, and 90%, respectively. Plasminogen activator inhibitor-1 and C-reactive protein levels increased with atherosclerosis and thrombosis triggering. Maximal standardized uptake value at baseline was 0.62Ϯ0.13, 0.96Ϯ0.33 at the middle of feeding, and 1.06Ϯ0.38 at the end of feeding. Segments that developed thrombosis had the highest maximal standardized uptake value of 1.32Ϯ0.69 (113% increase; Pϭ0.002) and had a 129% increase in macrophage density compared with segments without thrombi (Pϭ0.01). Conclusions-Fluorodeoxyglucose uptake was proportional to the duration of cholesterol feeding and peaked with plaque disruption and thrombosis. CTA was highly accurate in detecting thrombi. Our findings in this animal model of atherosclerotic plaques with high macrophage density showed that CTA/positron emission tomography can be used to identify and localize inflamed plaques and thrombosis. With the currently available technology and nuclear tracers, however, many challenges remain before clinical applications are possible.
Predicting the occurrence of future acute coronary syndromes remains an important challenge of contemporary cardiology. It is thought that detecting the individual vulnerable plaques in patients can be an important step to preventing myocardial infarction and sudden cardiac death. Coronary angioscopy can provide detailed information of the luminal surface of plaque, such as color, thrombus, or disruption, and is one of a few possibly useful imaging modalities for identifying vulnerable plaques. During its 20-year history, coronary angioscopy has been used as a diagnostic tool or to guide coronary angioplasty, and has contributed to our understanding of the pathophysiology of coronary artery disease. Yellow plaques seen during angioscopy seem to have many characteristics of high risk or vulnerable plaques, most consistent with the thin-cap fibroatheroma. Moreover, differences in yellow color have been reported to reflect differences in the structure or composition of plaques. Development of quantitative methods to assess plaque color and histopathologic correlations in conjunction with prospective natural history studies may lead to advances in vulnerable plaque detection by coronary angioscopy. Although current angioscopic devices are limited by the need to displace the column of blood in order to see the vessel wall, and by the lack of quantitative colorimetric methods, advances in technology may lead to new device versions that could be practical for expanded clinical use.
The results show a computer-based neural network can perform as well as expert readers working under optimal conditions including full knowledge of the patient's clinical, prior angiographic and stress test data. Thus, the method is promising as a diagnostic aid to the recognition of ischemic heart disease in the clinical setting of treadmill exercise testing in conjunction with myocardial perfusion imaging.
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