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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:1312.)
© 2003 American Heart Association, Inc.

Editorials

Hydrolytic Enzymes Released From Resident Macrophages and Located in the Intima Extracellular Matrix as Agents That Modify Retained Apolipoprotein B Lipoproteins

Germán Camejo

From AstraZeneca Discovery, Mölndal, and Wallenberg Laboratory, Gothenburg University, Sahlgrenska Academy, Sweden.

Correspondence to Germán Camejo, AstraZeneca Discovery, Mölndal S 43183, Sweden. E-mail german.camejo@astrazeneca.com

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Identification of the molecular mechanisms causing the focal response of arterial cells that induce atherosclerotic lesions may open new therapeutic venues for prevention of this disease. Many of the products that appear to trigger the tissue reaction originate from apolipoprotein B (apoB)-lipoproteins retained in the intima extracellular matrix. These may be key phenomena contributing to the initial and late phases of atherosclerotic plaque development.^1–4 The preferential retention of apoB-lipoproteins, especially LDL, can lead to direct modifications of the labile structure of these complex particles and furthermore could provide the time required for enzymatic and nonenzymatic more profound alterations of their lipid and protein moieties.^3,4 Such structural changes may produce lipid and peptide neo-epitopes, lipid hydrolytic, and oxidative products with potent biological effects. Degradation of the apoB-100 and the polar lipid surface components can also lead to aggregation and fusion of lipoprotein particles that eventually form part of the complex array of extracellular lipid aggregates that grow with the progress of lesions.⁵ The structural and enzymatic agents that could contribute to such alterations in the extracellular intima may pre-exist there, like the proteoglycans, or could be secreted by macrophages and other intima-residing cells. These modifications may be part of a physiological scavenging process for removal of undesirable lipoprotein components. However, with elevated circulating levels of apoB-lipoproteins, especially at sites where intimal thickening occurs by matrix expansion, the beneficial scavenging process may become insufficient and may turn into an atherogenic cycle.⁶ Identification of the specific pathways that modify apoB-lipoproteins in the intima . . . [Full Text of this Article]

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