Small Coronary Calcium Deposits and Elevated Plasma Levels of Oxidized Low Density Lipoprotein are Characteristic of Acute Myocardial Infarction

Ehara, Shoichi; Naruko, Takahiko; Shirai, Naoya; Itoh, Akira; Hai, Eishu; Sugama, Yoshimi; Ohsawa, Masahiko; Okuyama, Takuhiro; Shirai, Nobuyuki; Yamashita, Hiroyuki; Itabe, Hiroyuki; Haze, Kazuo; Yoshiyama, Minoru; Ueda, Makiko

doi:10.5551/jat.e523

Cited by 12 publications

(8 citation statements)

References 25 publications

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“…Ox-LDL contributes to vascular calcification by inducing smooth muscle cells and foam cells to initiate fibrosis and form atheromas, which is followed by an increase in calcium deposition [16] . There is a positive correlation between coronary calcium or instability of coronary plaques and plasma ox-LDL level [17] . In vitro ox-LDL increased ALP activity, induced transient and strong expression of bone morphogenetic protein 2 (BMP2) and matrix gla-protein (MGP) and accelerated mineralization [18] .…”

Section: Discussionmentioning

confidence: 99%

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

Liu

Chen

et al. 2011

Acta Pharmacol Sin

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Aim: To investigate the ability of ox-LDL to induce ossification of endothelial progenitor cells (EPCs) in vitro and explored whether oxidative stress, especially hypoxia inducible factor-1α (HIF-1α) and reactive oxygen species (ROS), participate in the ossific process. Methods: Rat bone marrow-derived endothelial progenitor cells (BMEPCs) were cultured in endothelial growth medium supplemented with VEGF (40 ng/mL) and bFGF (10 ng/mL). The cells were treated with oxidized low-density lipoprotein (ox-LDL, 5 µg/mL) and/or β-glycerophosphate (β-GP, 10 mmol/L). Calcium content and Von Kossa staining were used as the measures of calcium deposition. Ossific gene expression was determined using RT-PCR. The expression of osteocalcin (OCN) was detected with immunofluorescence. Alkaline phosphatase (ALP) activity was analyzed using colorimetric assay. Intercellular reactive oxygen species (ROS) were measured with flow cytometry. Results: BMEPCs exhibited a spindle-like shape. The percentage of cells that expressed the cell markers of EPCs CD34, CD133, and kinase insert domain-containing receptor (KDR) were 46.2%±5.8%, 23.5%±4.0%, and 74.3%±8.8%, respectively. Among the total cells, 78.3%±4.2% were stained with endothelial-specific fluorescence. Treatment of BMEPCs with ox-LDL significantly promoted calcium deposition, which was further significantly enhanced by co-treatment with β-GP. The same treatments significantly increased the gene expression of core-binding factor a-1 (cbfa-1) and OCN, while decreased the gene expression of osteoprotegerin (OPG). The treatments also significantly enhanced the activity of ALP, but did not affect the number of OCN + cells. Furthermore, the treatments significantly increased ROS and activated the hypoxia inducible factor-1α (HIF-1α). In all these effects, ox-LDL acted synergistically with β-GP. Conclusion: Ox-LDL and β-GP synergistically induce ossification of BMEPCs, in which an oxidizing mechanism is involved.

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Section: Discussionmentioning

confidence: 99%

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

Liu

Chen

et al. 2011

Acta Pharmacol Sin

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“…In addition to plaque instability, another crucial issue regarding diabetic macrovascular complications appears to be vascular stiffness, which is partially associated with calcification. The complexity of vulnerability and calcification appears to lead to the onset of acute coronary syndromes in DM, as Ehara et al have shown recently 34) . The present study did not examine calcificationrelated molecular expression combined with MMPs and apoptosis.…”

Section: Discussionmentioning

confidence: 91%

Advanced Glycation End Product-Mediated Matrix Metallo-proteinase-9 and Apoptosis via Renin-Angiotensin System in Type 2 Diabetes

Ishibashi

Kawaguchi

Sugimoto

et al. 2010

JAT

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Aim: Advanced glycation end products (AGE) play a key role in diabetic vascular complications, whereas matrix metalloproteinases (MMPs) and apoptosis contribute to plaque instability. This study was conducted to investigate the association of AGE-mediated MMP-9 and apoptosis with the renin−angiotensin system (RAS). We also examined the correlation between plasma HbA1c levels and plaque parameters. Methods: We used autopsy specimens from the aortae and coronary arteries of patients with or without diabetes (n 11, each group) for the immunohistochemistry of AGE, MMP-9, angiotensin-converting enzyme (ACE), and the receptor for AGE (RAGE). Apoptosis was determined by TUNEL staining. Results: The proportions of AGE accumulation, MMP-9 expression and apoptosis in intimal areas of both aortic and coronary specimens of diabetics were greater than in nondiabetics. MMP-9 expression and apoptosis were correlated with AGE accumulation. RAGE expression was significantly increased in diabetic specimens compared to nondiabetes. Interestingly, the expression of ACE in diabetic specimens was increased and also correlated with AGE accumulation, RAGE expression, MMP-9 expression, and apoptosis in all specimens from diabetics and nondiabetics. Plasma levels of HbA1c were linearly correlated with AGE accumulation, MMP-9, apoptosis, and ACE expression. Conclusion: The present study shows that AGE/RAGE-related MMP-9 expression and apoptosis were correlated with ACE expression in diabetic plaques and that RAS may be involved in AGEdependent diabetic vascular complications. J Atheroscler Thromb, 2010; 17:578-589.

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“…Oxidation of LDL has been suggested as a causal factor of human atherosclerosis 6,7,30) . Oxidatively modified LDL is a potent ligand for scavenger receptors on macrophages and thus contributes to the generation of macrophage-derived foam cells, the hallmark of early atherosclerotic fatty streak lesions 6, 7)…”

Section: Discussionmentioning

confidence: 99%

HDL2 Can Inhibit Further Oxidative Modification of Partially Oxidized LDL

Sakuma

Saeki

Itô

et al. 2010

JAT

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Aim: To investigate whether HDL2 can inhibit further oxidative modification of partially oxidized LDL (ox-LDL) by interrupting the chain oxidation reaction after lipid hydroperoxides (LOOH) formation. Methods: Following incubation of LDL 400 g protein/mL phosphate-buffered saline with Cu 2 for 1.75 h (defined as 0 min), incubation was continued after adding HDL2 200 g protein/mL or HDL2 800 g protein/mL to give both ox-LDL HDL2 200 g protein/mL or ox-LDL HDL2 800 g protein/mL. As a control, ox-LDL 200 g protein/mL and native LDL were prepared. Each sample was subjected to agarose gel electrophoresis and the LOOH in each sample was measured. Results: When the electrophoretic mobility of native LDL was designated 1, the relative electrophoretic mobility (REM) of ox-LDL increased significantly over time.The REMs of ox-LDL HDL2 800 g protein/mL from 10 min to 9 h were significantly lower than the REM of ox-LDL at the respective times (p 0.01). LOOH of ox-LDL HDL2 800 g protein/mL at 1, 3, 6 and 9 h was significantly higher than LOOH in ox-LDL at the respective times (p 0.01). The results of ox-LDL HDL2 200 g protein/mL were almost the same but to a lesser extent than the results of ox-LDL HDL2 800 g protein/mL. Conclusion:The present findings suggest that HDL2 can inhibit further oxidative modification of partially oxidized LDL by interrupting the chain oxidation reaction after LOOH formation in a concentration-dependent manner. J Atheroscler Thromb, 2010; 17:229-234.

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Small Coronary Calcium Deposits and Elevated Plasma Levels of Oxidized Low Density Lipoprotein are Characteristic of Acute Myocardial Infarction

Cited by 12 publications

References 25 publications

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

Oxidized low-density lipoprotein and β-glycerophosphate synergistically induce endothelial progenitor cell ossification

Advanced Glycation End Product-Mediated Matrix Metallo-proteinase-9 and Apoptosis via Renin-Angiotensin System in Type 2 Diabetes

HDL2 Can Inhibit Further Oxidative Modification of Partially Oxidized LDL

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