Oxidized Low-Density Lipoprotein and Atherogenesis

Fig. 12.1

Sudan red stained aorta (left) of hyperlipidemic rabbit compared to radiograph of same after injection of 90 μCi ¹²⁵I-MDA2 (right) (Reproduced with kind permission of Springer Science + Businesss Media from Tsimikas et al. [19])

This same radio-labeled antibody has also been used in subsequent experiments to demonstrate the eventual regression of atherosclerotic plaque through a modified diet [12–14].

Gamma camera scintigraphy of hyperlipidemic rabbits with ^99mTc-MDA2 has also been used to successfully demonstrate areas of increased deposition of oxLDL [13] (Fig. 12.2).

Fig. 12.2

(a, b) Scintigraphy with ^99mTc-MDA2 with corresponding sudan red-stained aorta in hyperlipidemic rabbit (a) as compared to a normal rabbit (b) (Reproduced with permission of Elsevier from Tsimikas [13])

Radio-labeled (¹²⁵I) native, non-modified LDL in humans successfully imaged known carotid atherosclerotic disease in humans [15].

Oxidized LDL was radio-labeled with ^99mTc and used in patients who had recently suffered a transient ischemic attack. Carotid arteries with atherosclerotic plaque had significantly more uptake of the radio-labeled LDL than normal carotids [16].

Future Directions

Native and oxLDL have successfully been labeled with fluorine-18. An obvious application of ¹⁸F labeled oxLDL would be the assessment of plaque vulnerability in patients at risk for atherosclerosis by PET scanning [17]. To date, neither PET nor MRI [18] have been used for the imaging of oxLDL.

References

Choi SH, Chae A, Miller E, Messig M, Ntanios F, DeMaria AN, Nissen SE, Witztum JL, Tsimikas S. Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of Atherosclerosis with Aggressive Lipid Lowering) study. J Am Coll Cardiol. 2008;52:24–32.PubMedCrossRef

Tsimikas S. Oxidized low-density lipoprotein biomarkers in atherosclerosis. Curr Atheroscler Rep. 2006;8:55–61.PubMedCrossRef

Tsimikas S, Palinski W, Witztum JL. Atherosclerosis and lipoproteins: circulating autoantibodies to oxidized LDL correlate with arterial accumulation and depletion of oxidized LDL in LDL receptor–deficient mice. Arterioscler Thromb Vasc Biol. 2001;21:95–100.PubMedCrossRef

Tsimikas S, Brilakis ES, Miller ER, McConnell JP, Lennon RJ, Kornman KS, Witztum JL, Berger PB. Oxidized phospholipids, Lp(a) lipoprotein, and coronary artery disease. N Engl J Med. 2005;353:46–57.PubMedCrossRef

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