Role of T Lymphocytes in the Pathogenesis of Atherosclerosis: Animal Studies Using Athymic Nude Rats

Haraoka, Seiji; Shimokama, Tatsuro; Watanabe, Teruo

doi:10.1111/j.1749-6632.1997.tb52034.x

Cited by 6 publications

(2 citation statements)

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“…Electron microscopic studies of human atherosclerotic lesions have revealed that there is an intimate interaction between T cells and macrophages and that the T cells involved in this interaction are usually in the activated state as they express major histocompatibility complex (MHC) class II antigen. We demonstrated that in hypercholesterolemic rats, T cells actually predominate in the incipient phase (cholesterol-rich diet for 2 weeks) of the lesion formation and are gradually surpassed by monocyte infiltration in later stages (9,10). Therefore, one can envision that these T cells are not simply bystanders in the lesions, but instead actively participate in the lesion progression, possibly through the release of diverse cytokines (9,11,12).…”

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confidence: 95%

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Fan

Watanabe

2003

J Atheroscler Thromb

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302

184

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Atherosclerosis and its complications constitute the most common causes of death in Western societies and Japan. Although several theories or hypotheses about atherogenesis have been proposed during the past decades, none can completely explain the whole process of the pathogenesis of atherosclerosis because this disease is associated with multiple risk factors. In spite of this, the concept that atherosclerosis is a specific form of chronic inflammatory process resulting from interactions between plasma lipoproteins, cellular components ( monocyte/macrophages, T lymphocytes, endothelial cells and smooth muscle cells ) and the extracellular matrix of the arterial wall, is now well accepted. Histologically, atherosclerotic lesions from the early-stage ( fatty streak ) to more complicated lesions possess all the features of chronic inflammation. It has been demonstrated that atherogenic lipoproteins such as oxidized low density lipoprotein ( LDL ), remnant lipoprotein (β -VLDL) and lipoprotein [ Lp ] ( a ) play a critical role in the pro-inflammatory reaction, whereas high density lipoprotein ( HDL ), anti-atherogenic lipoproteins, exert anti-inflammatory functions. In cholesterol-fed animals, the earliest events in the arterial wall during atherogenesis are the adhesion of monocytes and lymphocytes to endothelial cells followed by the migration of these cells into the intima. It has been shown that these early events in atherosclerosis are triggered by the presence of high levels of atherogenic lipoproteins in the plasma and are mediated by inflammatory factors such as adhesion molecules and cytokines in the arterial wall. The development of genetically modified laboratory animals ( transgenic and knock-out mice and transgenic rabbits ) has provided a powerful approach for dissecting individual candidate genes and studying their cause-and-effect relationships in lesion formation and progression. The purpose of this article is to review the recent progress regarding the inflammatory processes during the development of atherosclerosis based on both human and experimental studies. In particular, we will address the mechanisms of atherogenic lipoproteins in terms of inflammatory reactions associated with hypercholesterolemia. Understanding the molecular mechanisms responsible for inflammatory reactions during atherogenesis may help us to develop novel therapeutic strategies to control, treat and prevent atherosclerosis in the future. J Atheroscler Thromb, 2003; 10: 63-71.

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confidence: 95%

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Fan

Watanabe

2003

J Atheroscler Thromb

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302

184

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“…Activated Tcells surround and influence macrophages/foam cells by the production of other pro-inflammatory cytokines. Especially in the incipient phase of lesion formation, T-cells seem to play an important role by orchestrating monocyte infiltration [16,17].…”

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confidence: 99%

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Schroecksnadel

Frick²,

Winkler³

et al. 2006

CVP

126

102

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Inflammation and immune activation are crucially involved in the pathogenesis of atherosclerosis and cardiovascular disease. Accordingly, markers of inflammation such as fibrinogen, ferritin, C-reactive protein or neopterin are found in patients with vascular diseases, correlating strongly with the extent of disease and predicting disease progression. Neopterin formation by human monocyte-derived macrophages and dendritic cells is induced by the pro-inflammatory cytokine interferon-gamma, which is released by activated T-lymphocytes. Human macrophages are centrally involved in plaque formation, and interferon-gamma and macrophages are also of importance in the development of oxidative stress for antimicrobial and antitumoural defence within the cell-mediated immune response. Interferon-gamma also stimulates the enzyme indoleamine-2,3-dioxygenase, which degrades tryptophan to kynurenine. Again, macrophages are the most important cell type executing this enzyme reaction, but also other cells like dendritic cells, endothelial cells or fibroblasts can contribute to the depletion of tryptophan. Likewise, enhanced tryptophan degradation was reported in patients with coronary heart disease and was found to correlate with enhanced neopterin formation. In chronic diseases such as in cardiovascular disease, biochemical reactions induced by interferon-gamma may have detrimental consequences for host cells. In concert with other pro-inflammatory cytokines, interferon-gamma is the most important trigger for the formation and release of reactive oxygen species (ROS). Chronic ROS-production leads to the depletion of antioxidants like vitamin C and E and glutathione, with a consequence that oxidative stress develop. Oxidative stress plays a major role in the atherogenesis and progression of cardiovascular disease, and it may also account for the irreversible oxidation of other oxidation-sensitive substances like B-vitamins (e.g. folic acid and B12). They are essential cofactors in homocysteine-methionine metabolism. Associations between moderate hyperhomocysteinaemia and cellular immune activation are found in several diseases including coronary heart disease, and data indicate that hyperhomocysteinaemia may develop as a consequence of immune activation. Homocysteine accumulation in the blood is established as an independent risk factor for cardiovascular disease. Homocysteine itself has the capacity to further enhance oxidative stress. Interferon-gamma appears to be a central player in atherogenesis and in the development and progression of cardiovascular disease. Anti-inflammatory and immunosuppressive treatment (e.g. with non-steroidal anti-inflammatory drugs or statins) may among other consequences, also contribute to a slow-down of the adverse effects of interferon-gamma.

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Anatomie und Pathologie der Koronararterien

Hort¹,

Schwartzkopff²

2000

Pathologie Des Endokard, Der Kranzarterien Und Des Myokard

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Role of T Lymphocytes in the Pathogenesis of Atherosclerosis: Animal Studies Using Athymic Nude Rats

Cited by 6 publications

References 6 publications

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease

Anatomie und Pathologie der Koronararterien

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Role of T Lymphocytes in the Pathogenesis of Atherosclerosis: Animal Studies Using Athymic Nude Rats

Cited by 6 publications

References 6 publications

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Inflammatory Reactions in the Pathogenesis of Atherosclerosis

Crucial Role of Interferon-&#947; and Stimulated Macrophages in Cardiovascular Disease

Anatomie und Pathologie der Koronararterien

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Crucial Role of Interferon-γ and Stimulated Macrophages in Cardiovascular Disease