Oxidized low‐density lipoprotein is chemotactic for arterial smooth muscle cells in culture

Autio, I; Jaakkola, Olli; Solakivi, Tiina; Nikkari, T.

doi:10.1016/0014-5793(90)80857-f

Cited by 78 publications

(42 citation statements)

References 15 publications

(15 reference statements)

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“…This order of activity is consistent with that seen for chemoattraction of human monocytes (46). It is noteworthy that the same lipids that stimulate movement of monocytes, T-lymphocytes, and smooth muscle cells (23), inhibit movement of EC. In contrast, Kume et al (40) have shown that the induction of EC adhesion molecules by lysoPE (and lysoPC) is significantly higher than by lysoPI (and lysoPS).…”

Section: Discussionsupporting

confidence: 86%

“…Metal ion-oxidized LDL is characterized by altered chemical and physical properties including elevated levels of cholesterol, a diverse array of oxidized sterols and fatty acids, lysophosphatidylcholine (lysoPC), degradation fragments of apo B-100, and increased flotation density and electrophoretic mobility (19). In addition to inducing foam cell formation in cultured macrophages (20), oxidized LDL has multiple properties that may contribute to the atherogenic process, e.g., it is chemotactic for blood monocytes (21), T-lymphocytes (22), and smooth muscle cells (23), and is cytotoxic to cultured cells including SMC (24) (see references 25 and 26 for reviews). Furthermore, recent biochemical and immunological studies indicate that oxidized LDL is present in atherosclerotic lesions (25), and may in fact be present in plasma (27).…”

Section: Introductionmentioning

confidence: 99%

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Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

Murugesan¹,

Fox²

1996

J. Clin. Invest.

104

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Endothelial cell (EC) movement is required for the development and repair of blood vessels. We have previously shown that LDL oxidized by transition metals almost completely suppressed the wound-healing migratory response of vascular EC in vitro. We now report that lysophosphatidylcholine (lysoPC), a lipid component of oxidized LDL, has an important role in the antimigratory activity of the lipoprotein. Purified 1-palmitoyl lysoPC inhibited movement with a halfmaximal activity at 12-15 M, and near complete inhibition at 20 M; the inhibitory concentration of lysoPC was consistent with its abundance in oxidized LDL. The inhibition was not due to cytotoxicity since protein synthesis was unaffected and since EC movement was restored after removal of lysoPC. Lysophospholipid activity was dependent on lipid structure. LysoPC's containing 1-position C 16 or C 18 saturated fatty acids were antimigratory, but those containing C Յ 14 saturated fatty acids or polyunsaturated fatty acids were not. The activity of 1-palmitoyl lysolipids with various head groups was examined. Lysophosphatidylinositol was more antimigratory than lysophosphatidylglycerol and lysophosphatidylcholine, which were more potent than lysophosphatidylserine and lysophosphatidylethanolamine. Monoglyceride was inactive while lysophosphatidate had promigratory activity. These results are consistent with head group size rather than charge as a critical determinant of activity. To show that lysophospholipids within an intact lipoprotein were active, LDL was treated with bee venom phospholipase A 2 (PLA 2 ). The modified lipoprotein inhibited EC movement to the same extent as iron-oxidized LDL and antimigratory activity correlated with the amount of lysoPC formed. To determine antimigratory activity of lysoPC present in oxidized LDL, lipid extracts from oxidized LDL were fractionated by normal phase HPLC. The fraction comigrating with lysoPC had nearly the same activity as the total extract confirming that lysoPC (or a co-eluting lipid) was a major antimigratory molecule in oxidized LDL. These studies demonstrate that lysoPC

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

Murugesan¹,

Fox²

1996

J. Clin. Invest.

104

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“…Ox-LDL has been shown to be chemotactic for arterial smooth muscle cells in culture, whereas N-LDL is without significant activity. 10 It has been demonstrated that peroxidation of LDL is dependent on low concentrations of copper or iron and, in consequence, is inhibited by EDTA or antioxidants such as butylated hydroxytoluene and vitamin E. 11 -13 To date, the mechanisms for the increased atherogenic potential induced by oxidation are unclear.…”

Section: Oxidation Of Low Density Lipoprotein Enhances Its Potential mentioning

confidence: 99%

Oxidation of low density lipoprotein enhances its potential to increase intracellular free calcium concentration in vascular smooth muscle cells.

Weisser

Locher

Mengden

et al. 1992

Arterioscler Thromb

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“…35,36 The same lipids that inhibit movement of endothelial cells stimulate movement of monocytes, T lymphocytes, and smooth muscle cells. 37,38 The mentioned inflammatory cells play a crucial role in the development of atherosclerosis. 39 Recently, it was proposed that inflammatory responses involved in atherosclerotic plaque progression also contribute to collateral formation.…”

Section: Van Weel Et Al Lipids Affect Arteriogenesis More Than Glucosementioning

confidence: 99%

Hypercholesterolemia Reduces Collateral Artery Growth More Dominantly Than Hyperglycemia or Insulin Resistance in Mice

Weel

Vries

Voshol

et al. 2006

ATVB

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Objective-Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or disturbed lipid metabolism on arteriogenesis. Methods and Results-Femoral artery occlusion was performed in streptozotocin(STZ)-treated mice, nonobese diabetic (NOD) mice, and insulin-resistant Ob/Ob mice on regular diet, and APOE3*Leiden mice on different hypercholesterolemic diets. Angiography and laser Doppler perfusion analysis of hindlimbs were performed postoperatively. Surprisingly, angiographic arteriogenesis was not impaired in diabetic and insulin-resistant mice. Perfusion recovery in STZ-treated and Ob/Ob mice was only decreased by 19% and 16%, respectively (PϽ0.05). Furthermore, perfusion recovery was unchanged between high-glycemic and mild-glycemic NOD mice. Angiographic arteriogenesis in APOE3*Leiden mice, however, was markedly impaired at 7 days and 14 days (PՅ0.01). Correspondingly, perfusion recovery was 41% decreased in APOE3*Leiden mice (PϽ0.05). There was an inverse correlation of perfusion recovery with plasma cholesterol (Pϭ0.02), but not with triglyceride, free fatty acid, glucose, or insulin levels. Conclusions-Hypercholesterolemia reduces arteriogenesis more dominantly than hyperglycemia or hyperinsulinemia in mice. This suggests that a disturbed lipid metabolism as observed in diabetic patients might be crucial for the impairment of collateral formation. Key Words: arteriogenesis Ⅲ cholesterol Ⅲ collateral circulation Ⅲ diabetes Ⅲ NOD mice Ⅲ peripheral vascular disease H yperlipidemia and diabetes mellitus are 2 major risk factors for coronary and peripheral arterial disease, in addition to nicotine abuse, hypertension, and other factors, by increasing the progression of atherosclerosis. 1 Moreover, collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial occlusive disease, 2,3 is deregulated by both hyperlipidemia 4 -8 and diabetes. 9,10 Poor arteriogenesis may influence the rate of disease progression and susceptibility for therapeutic intervention, such as direct revascularization techniques, exercise training, or experimental therapies to promote arteriogenesis. 11,12 Because both hyperlipidemia and diabetes often coexist in patients with arterial obstructive disease, it is difficult to determine which risk factor plays a predominant role in the impairment of collateral formation.Moreover, evidence is accumulating that a disturbed lipid metabolism is a crucial determinant of the development of diabetes and its complications, such as accelerated atherosclerosis. For example, disordered fat storage and mobilization, mainly involving triglyceride and free fatty acid metabolism, were implicated in the pathogenesis of insulin resistance and type 2 diabetes. [13][14][15][16][17][18] Furthermore, considerable attention has been drawn to the glycation and/...

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Oxidized low‐density lipoprotein is chemotactic for arterial smooth muscle cells in culture

Cited by 78 publications

References 15 publications

Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

Role of lysophosphatidylcholine in the inhibition of endothelial cell motility by oxidized low density lipoprotein.

Oxidation of low density lipoprotein enhances its potential to increase intracellular free calcium concentration in vascular smooth muscle cells.

Hypercholesterolemia Reduces Collateral Artery Growth More Dominantly Than Hyperglycemia or Insulin Resistance in Mice

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