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Atherosclerosis, Hypertension and Diabetes pp 53–62Cite as

Biochemical Mechanisms of Hyperhomocysteinemia in Atherosclerosis: Role of Chemokine Expression

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 8))

Abstract

Abundant epidemiological evidence has demonstrated that hyperhomocysteinemia is a common and independent risk factor for cardiovascular disorders due to atherosclerosis. Monocyte infiltration into the subendothelial space in the arterial wall and later differentia-tion into macrophages are important initial steps in the development of atherosclerotic lesions. Macrophages can then take up large amount of lipids to form foam cells in the lesion. The findings that macrophages and foam cells accumulate in the atherosclerotic lesions of hyper-homocysteinemic patients suggest that the recruitment of monocytes is enhanced during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates migration of monocytes into the intima of arterial walls. The level of MCP-1 is increased in atherosclerotic lesions in both human and experimental animals. MCP-1 exerts its action mainly through the interaction with C-C chemokine receptor (CCR2) on the surface of monocytes. In this article, we reviewed recent studies on the homocysteine-induced MCP-1 and its receptor CCR2 expression in vascular cells as well as the involvement of oxidative stress and nuclear factor kappa B (NF-KB) activation. Homocysteine-stimulated CCR2 expression in monocytes together with increased MCP-1 expression in vascular cells may represent a mechanism for homocysteine-enhanced monocyte infiltration into the arte-rial wall during atherogenesis.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, University of Hong Kong, Hong Kong, People’s Republic of China

    O. Karmin MB, PHD & Yaw L. Siow PHD

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  1. O. Karmin MB, PHD
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  2. Yaw L. Siow PHD
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Editors and Affiliations

  1. Division of Stroke & Vascular Disease, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

  2. Department of Medicine, Jikei University School of Medicine, Tokyo, Japan

    Makoto Nagano MD, PhD (Professor Emeritus) (Professor Emeritus)

  3. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Peter Zahradka PhD (Associate Professor) & Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Associate Professor) &  (Distinguished Professor and Director)

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Karmin, O., Siow, Y.L. (2003). Biochemical Mechanisms of Hyperhomocysteinemia in Atherosclerosis: Role of Chemokine Expression. In: Pierce, G.N., Nagano, M., Zahradka, P., Dhalla, N.S. (eds) Atherosclerosis, Hypertension and Diabetes. Progress in Experimental Cardiology, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9232-1_4

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  • DOI: https://doi.org/10.1007/978-1-4419-9232-1_4

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