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Atherosclerosis: pathogenesis and key cellular processes, current and emerging therapies, key challenges, and future research directions

Chan, Yee-Hung and Ramji, Dipak P. 2022. Atherosclerosis: pathogenesis and key cellular processes, current and emerging therapies, key challenges, and future research directions. In: Ramji, Dipak ed. Atherosclerosis: Methods and Protocols, Vol. 2419. Methods in Molecular Biology, New York, NY: Springer, pp. 3-19. (10.1007/978-1-0716-1924-7_1)

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Abstract

Atherosclerosis is the principal cause of cardiovascular disease that continues to be a substantial drain on healthcare systems, being responsible for about 31% of all global deaths. Atherogenesis is influenced by a range of factors, including oxidative stress, inflammation, hypertension, and hyperlipidemia, and is ultimately driven by the accumulation of low-density lipoprotein cholesterol within the arterial wall of medium and large arteries. Lipoprotein accumulation stimulates the infiltration of immune cells (such as monocytes/macrophages and T-lymphocytes), some of which take up the lipoprotein, leading to the formation of lipid-laden foam cells. Foam cell death results in increased accumulation of dead cells, cellular debris and extracellular cholesterol, forming a lipid-rich necrotic core. Vascular smooth muscle cells from the arterial media also migrate into the intima layer and proliferate, taking up the available lipids to become foam cells and producing extracellular matrix proteins such as collagen and elastin. Plaque progression is characterized by the formation of a fibrous cap composed of extracellular matrix proteins and smooth muscle cells, which acts to stabilize the atherosclerotic plaque. Degradation, thinning, and subsequent rupture of the fibrous cap leads to lumen-occlusive atherothrombosis, most commonly resulting in heart attack or stroke. This chapter describes the pathogenesis of atherosclerosis, current and emerging therapies, key challenges, and future directions of research.

Item Type: Book Section
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Springer
ISBN: 9781071619230
ISSN: 1064-3745
Last Modified: 10 Mar 2022 12:18
URI: https://orca.cardiff.ac.uk/id/eprint/148040

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