Lipoprotein-like Phospholipid Particles Inhibit the Smooth Muscle Cell Cytotoxicity of Lysophosphatidycholine and Platelet-Activating Factor

Nilsson, Jan; Dahlgren, Britt; Ares, Mikko P.S.; Westman, Jan; Nilsson, Anna; Cercek, Bojan; Shah, Prediman K.

doi:10.1161/01.atv.18.1.13

Cited by 25 publications

(9 citation statements)

References 43 publications

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“…Consistent with previous observations, 12,13 LPC and ROS were found to be toxic to cells at high concentrations, whereas lower concentrations induced DNA synthesis and cell growth. Similar effects have been observed with moxLDL, which over a narrow concentration range can cause both proliferative and cytotoxic effects.…”

Section: Discussionsupporting

confidence: 92%

Lysophosphatidylcholine and Reactive Oxygen Species Mediate the Synergistic Effect of Mildly Oxidized LDL With Serotonin on Vascular Smooth Muscle Cell Proliferation

et al. 2001

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Background-Mild oxidation of LDL enhances its atherogenic potential and induces a synergistic interaction with serotonin (5HT) on vascular smooth muscle cell (VSMC) proliferation. Because of its complex chemical nature, the mitogenic components of mildly oxidized LDL (moxLDL) remain unclear. , and 5HT stimulated DNA synthesis in a dose-dependent manner. MoxLDL had a maximal stimulatory effect at a concentration of 5 g/mL (211%), LPC at 15 mol/L (156%), H 2 O 2 at 5 mol/L (179%), and 5HT at 50 mol/L (205%). Added together, moxLDL (50 ng/mL) and 5HT (50 mol/L) synergistically increased DNA synthesis (443%). Coincubation of LPC (1 mol/L) with H 2 O 2 (0.5 mol/L) and 5HT (5 mol/L) resulted in a synergistic increase in DNA synthesis (439%), which was nearly equal to that of moxLDL with 5HT (443%). The combined effects of LPC, H 2 O 2 , and 5HT on DNA synthesis were completely reversed by the combined use of an antioxidant, N-acetylcysteine (400 mol/L) or butylated hydroxytoluene (20 mol/L), with a 5HT 2 receptor antagonist, LY281067 (10 g/mL). Conclusions-Our results suggest that both LPC and reactive oxygen species may contribute to the mitogenic effect of moxLDL on VSMCs and its synergistic effect with 5HT.

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Section: Discussionsupporting

confidence: 92%

Lysophosphatidylcholine and Reactive Oxygen Species Mediate the Synergistic Effect of Mildly Oxidized LDL With Serotonin on Vascular Smooth Muscle Cell Proliferation

et al. 2001

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“…Another potential mechanism might be antagonism of phosphatidylcholine degradation to lysophosphatidylcholine (LPC), as shown in cultures of human smooth muscle cells [31].…”

Section: Restenosismentioning

confidence: 99%

Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases

Calabresi

Sirtori²,

Paoletti³

et al. 2006

Curr Atheroscler Rep

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Apolipoprotein A-I(Milano) (apoA-I(M)) is a natural variant of apoA-I characterized by a cysteine for arginine substitution at position 173 of the primary sequence. ApoA-I(M) carriers have much less atherosclerosis than expected from their very low plasma high-density lipoprotein (HDL) cholesterol levels, suggesting that the variant might be protective. Synthetic HDL (sHDL) made with a recombinant form of the dimeric A-I(M) (A-I(M)/A-I(M)) and phospholipids given in single or multiple injections is effective in inducing the regression of atherosclerotic plaques, preventing arterial restenosis, and limiting cardiac dysfunction after ischemia/reperfusion injury. In a phase II trial in patients with acute coronary syndromes, a short-term treatment with A-I(M)/A-I(M) sHDL caused a remarkable reduction of atheroma burden. Although at early stages of drug development, A-I(M)/A-I(M) sHDL holds vast promise for the treatment of a variety of cardiovascular diseases in humans.

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“…54,55 Furthermore, in vitro studies have demonstrated that both wild-type apolipoprotein A-I and apolipoprotein A-I Milano reduce the proapoptotic effect of oxysterols (produced during LDL oxidation) on vascular smooth muscle cells, which may further help preserve the integrity of the smooth muscle cell-rich cap of the atherosclerotic plaque. 56 Wild-type plasma-derived HDL has also been shown to reduce neointimal thickening in a perivascular cuff-induced carotid arterial injury model in apolipoprotein E-null mice. 57 Because inflammation is thought to play an important role in arterial response to injury, the anti-inflammatory effects of HDL may be the underlying mechanism for the reduction in neointimal thickening.…”

Section: Strategies For Increasing Circulating And/or Arterial Wall Hmentioning

confidence: 99%

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

Shah¹,

Kaul²,

Nilsson³

et al. 2001

Circulation

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176

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Lipoprotein-like Phospholipid Particles Inhibit the Smooth Muscle Cell Cytotoxicity of Lysophosphatidycholine and Platelet-Activating Factor

Cited by 25 publications

References 43 publications

Lysophosphatidylcholine and Reactive Oxygen Species Mediate the Synergistic Effect of Mildly Oxidized LDL With Serotonin on Vascular Smooth Muscle Cell Proliferation

Lysophosphatidylcholine and Reactive Oxygen Species Mediate the Synergistic Effect of Mildly Oxidized LDL With Serotonin on Vascular Smooth Muscle Cell Proliferation

Recombinant apolipoprotein A-IMilano for the treatment of cardiovascular diseases

Exploiting the Vascular Protective Effects of High-Density Lipoprotein and its Apolipoproteins

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