Atheromatous plaque

NELKEN N A, COUGHLIN s R, GORDON D and WILCOX J N (1991) Monocyte chemoattractant protein-1 in human atheromatous plaques Journal of Clinical Investigation 88, 1121-7. 

Carotenoids and cardiovascular diseases — Numerous epidemiological studies aimed to study the relationship of carotenoids and cardiovascular diseases (CVDs) including coronary accident risk and stroke. It appeared then that observational studies, namely prospective and case-control studies, pointed to a protective effect of carotenoids on myocardial infarct and stroke, but also on some atherosclerosis markers such as intima media thickness (IMT) of the common carotid artery (CCA) and atheromatous plaque formation. 

In atherosclerosis, ox-LDL is taken up ultimately by macrophages and smooth muscle cells in the arterial intima. Once loaded with lipid, these cells have a foamy appearance when examined histologically. The accumulation of these so-called foam cells in the artery wall leads to the formation of fatty streaks , which can lead to atheromatous plaque formation and consequent coronary heart disease. 

Atheromatous plaques are loaded with lipid peroxide products... 

Endothelial dysfunction, inflammation, and the formation of fatty streaks contribute to the formation of atherosclerotic coronary artery plaques, the underlying cause of coronary artery disease (CAD). The predominant cause of ACS, in more than 90% of patients, is atheromatous plaque rupture, Assuring, or erosion of an unstable atherosclerotic plaque that occludes less than 50% of the coronary lumen prior to the event, rather than a more stable 70% to 90% stenosis of the coronary artery.3 Stable stenoses are characteristic of stable angina. 

Apostolopoulos J, Davenport P, Tipping PG. Interleukin-8 production by macrophages from atheromatous plaques. Arterioscler Thromb Vase Biol 1996 16(8) 1007-1012. 

The cause of ACS in more than 90% of patients is rapture, Assuring, or erosion of an unstable atheromatous plaque. Plaques most susceptible to rupture have an eccentric shape, thin fibrous cap, large fatty core, high content of inflammatory cells such as macrophages and lymphocytes, limited amounts of smooth muscle, and significant compensatory enlargement. 

Esaki, T., Hayashi, T, Muto, E., Kano, H., Kumar, T.N., Asai, Y., Sumi D., and Iguchi, A., 2000, Expression of nitric oxide synthase and Eas/Fas ligand correlates with the incidence of apoptosis cell death in atheromatous plaques ofhuman coronary arteries, Nitric Oxide 4 561-571. 

NO also reduces endothelial adhesion of monocytes and leukocytes, key features of the early development of atheromatous plaques. This effect is due to the inhibitory effect of NO on the expression of adhesion molecules on the endothelial surface. In addition, NO may act as an antioxidant, blocking the oxidation of low-density lipoproteins and thus preventing or reducing the formation of foam cells in the vascular wall. Plaque formation is also affected by NO-dependent reduction in endothelial cell permeability to lipoproteins. The importance of eNOS in cardiovascular disease is supported by experiments showing increased atherosclerosis in animals deficient in eNOS by pharmacologic inhibition. Atherosclerosis risk factors, such as smoking, hyperlipidemia, diabetes, and hypertension, are associated with decreased endothelial NO production, and thus enhance atherogenesis. 

Woodbum, K.W. et al. (1996) Phototherapy of cancer and atheromatous plaque with texaphyrins, Journal of clinical laser medicine surgery 14, 343-8. 

In conclusion, neovascularization seems to play an important role in the development of atheromatic plaques, especially in the process of destabilization. Inhibitors of plaque neovascularization are under animal and clinical investigation, In the following years, we can obtain safe results for the novel treatment of high-risk plaques. 

See color plate.) Microscopy with 405 nm excitation reveals red fluorescence from talaporfin (LSI l/NPe6) in macrophages within atheromatous plaque on abdominal aorta in hyper- cholesterolemic rabbit, 24 hours after 5mg/kg intra- venous administration. Note green autofluorescence from elastic fibers in adventitia with no detected LS11. Source Courtesy of Prof. K Aizawa, Tokyo Medical University, Tokyo, Japan. 

Spears JR, SerurJ, Shropshire D, Paulin S, Fluorescence of experimental atheromatous plaques with hematophorphyrin derivative, J Clin Invest I 983 71 395—399. 

I 5 Kessel D, Sykes E, Porphyrin accumulation by atheromatous plaques of the aorta, Photochem Photobiol 1984 40(1) 59-61. 

Hayashi J, Kuroiwa Y Sato H, et al. Transadventitial localization of atheromatous plaques by fluorescence emission spectrum analysis of mono-L-aspartyl chlorin e6. Cardiovasc Res 1993 27 1943-1947. 

If the clot forms on an atheromatous plaque in a coronary artery, myocardial infarction is imminent a thrombus in a deep leg vein can be dislodged and carried into a lung artery and can cause pulmonary embolism. 

Oxidative stress is now widely believed to be the major mechanism of athero-genesis. Interestingly, it was demonstrated 47 years ago that atheromatous plaques contain abundant lipoperoxides and other lipid peroxidation products (G9). More recently, our understanding of this process was advanced when evidence was provided for significant free radical activity and the lipid oxidative modification hypothesis was presented (P10). A subsequent study provided further evidence that oxidatively modified low-density lipoproteins (LDL) play a major role in the formation of the fatty streak, the earliest visible atherosclerotic lesion, and the subsequent production of the atheroscelrotic plaque (S27). The proposed sequence, which involves arterial endothelial and smooth muscle cells, as well as mono-cytes/macrophages, is as follows (Ql, S25). 

Atheromatous plaques are typically slow growing or quiescent for long periods but may suddenly develop fissures or ulcers (Fig. 6.5). Activated plaques trigger platelet aggregation. 

TIA, stroke or death as a result of dislodgement of atheromatous plaque by the catheter tip dissection of the arterial wall thrombus formation on the catheter tip air embolism... 

The surgical removal of atheromatous plaque from within the carotid artery is termed carotid endarterectomy. The operation was first performed in an attempt to improve the flow of blood to the brain, although no systematic attempt was made to assess the risks and benefits of the procedure. Subsequently, randomized trials were performed in patients with a history of recent symptomatic stroke, and also in those with asymptomatic disease, to determine whether the operation was beneficial and, if so, what the predictors of benefit would be. As a result of these trials, carotid endarterectomy has been proven to be an effective treatment for the secondary prevention of stroke in selected patients. 

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