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Trojan Horse Hypothesis: Inhaled Airborne Particles, Lipid Bullets, and AtherogenesisTrojan Horse Hypothesis: Inhaled Airborne Particles, Lipid Bullets, and Atherogenesis

JAMA. 2006;295(20):2354-2355. doi:10.1001/jama.295.20.2354-a
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AUTHOR INFORMATION

Letters Section Editor: Robert M. Golub, MD, Senior Editor.

TROJAN HORSE HYPOTHESIS: INHALED AIRBORNE PARTICLES, LIPID BULLETS, AND ATHEROGENESIS

To the Editor: In their Preliminary Communication, Dr Sun and colleagues1 showed that in apolipoprotein E knockout mice, exposure to concentrated ambient particles potentiated atherosclerosis under a condition of a high-fat diet. These observations suggest a Trojan horse hypothesis that could explain involvement of microparticles in atherogenesis.

Circulating lipid particles could serve as “lipid bullets” carrying lipophilic components or microspheric compounds such as airborne particles. These particles might infiltrate the intima, leading to enhanced plaque formation by inducing macrophage-mediated cytokine production and foam cell formation. Circulating lipoprotein particles (eg, apolipoprotein B [apo-B]-containing particles in the human postprandial state) loaded with lipophilic microparticles have been shown to transit endothelium and accumulate in the subendothelial matrix with subsequent engulfment by local macrophages.2 3

In contrast with “naked” apo-B–containing particles, which offer cholesterol to macrophages to maintain their functional structure, apo-B–containing lipoprotein particles loaded with lipophilic compounds, such as the inhaled 2.5-μm airborne particles in Sun et al, may disturb intracellular processes in subendothelial residing macrophages. Disruption of cellular metabolism inhibits prevention of apoptosis and activates proinflammatory pathways,4 factors that are present in an atherosclerotic lesion.5 6 A reduction of these loaded lipoprotein particles by statin therapy could additionally limit its biological activity (pleiotropic effects of statins).

In considering this hypothesis, it would be helpful if the authors could analyze the level of airborne particles in specific lipoprotein fractions and assess whether airborne particles are located in subendothelial macrophages.

Financial Disclosures: None reported.

References
Sun Q, Wang A, Jin X.  et al.  Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.  JAMA. 2005;2943003-3010
PubMed
Twickler T, Dallinga-Thie GM, Chapman MJ, Cohn JS. Remnant lipoproteins and atherosclerosis.  Curr Atheroscler Rep. 2005;7140-147
PubMed
Twickler TB, Dallinga-Thie GM, Cohn JS, Chapman MJ. Elevated remnant-like particle cholesterol concentration: a characteristic feature of the atherogenic lipoprotein phenotype.  Circulation. 2004;1091918-1925
PubMed
Tabas I. Cholesterol and phospholipid metabolism in macrophages.  Biochim Biophys Acta. 2000;1529164-174
PubMed
Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency.  Arterioscler Thromb Vasc Biol. 2005;252255-2264
PubMed
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease.  N Engl J Med. 2005;3521685-1695
PubMed

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Sun Q, Wang A, Jin X.  et al.  Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model.  JAMA. 2005;2943003-3010
PubMed
Twickler T, Dallinga-Thie GM, Chapman MJ, Cohn JS. Remnant lipoproteins and atherosclerosis.  Curr Atheroscler Rep. 2005;7140-147
PubMed
Twickler TB, Dallinga-Thie GM, Cohn JS, Chapman MJ. Elevated remnant-like particle cholesterol concentration: a characteristic feature of the atherogenic lipoprotein phenotype.  Circulation. 2004;1091918-1925
PubMed
Tabas I. Cholesterol and phospholipid metabolism in macrophages.  Biochim Biophys Acta. 2000;1529164-174
PubMed
Tabas I. Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency.  Arterioscler Thromb Vasc Biol. 2005;252255-2264
PubMed
Hansson GK. Inflammation, atherosclerosis, and coronary artery disease.  N Engl J Med. 2005;3521685-1695
PubMed
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