Journal of Atherosclerosis and Thrombosis
Online ISSN : 1880-3873
Print ISSN : 1340-3478
ISSN-L : 1340-3478
Volume 20 , Issue 10
Showing 1-5 articles out of 5 articles from the selected issue
Committee Report
Review
  • Maria F. Lopes-Virella, Gabriel Virella
    2013 Volume 20 Issue 10 Pages 743-754
    Published: 2013
    Released: October 28, 2013
    [Advance publication] Released: August 20, 2013
    JOURNALS FREE ACCESS
    There is strong evidence supporting a key role of the adaptive immune response in atherosclerosis, given that both activated Th cells producing predominantly interferon-γ and oxidized LDL (oxLDL) and the corresponding antibodies have been isolated from atheromatous plaques. Studies carried out using immune complexes (IC) prepared with human LDL and rabbit antibodies have demonstrated proatherogenic and pro-inflammatory properties, mostly dependent on the engagement of Fcγ receptors Ⅰ and Ⅱ in macrophages and macrophage-like cell lines. Following the development of a methodology for isolating modified LDL (mLDL) antibodies from serum and isolated IC, it was confirmed that antibodies reacting with oxLDL and advanced glycation end product-modified LDL are predominantly IgG of subtypes 1 and 3 and that mLDL IC prepared with human reagents possesses pro-inflammatory and proatherogenic properties. In previous studies, LDL separated from isolated IC has been analyzed for its modifications, and the reactivity of antibodies isolated from the same IC with different LDL modifications has been tested. Recently, we obtained strong evidence suggesting that the effects of mLDL IC on phagocytic cells are modulated by the composition of the mLDL. Clinical studies have shown that the level of mLDL in circulating IC is a strong predictor of cardiovascular disease (CVD) and, in diabetic patients, other significant complications, such as nephropathy and retinopathy. In conclusion, there is convincing ex vivo and clinical data supporting the hypothesis that, in humans, the humoral immune response to mLDL is pathogenic rather than protective.
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Original Article
  • Aya Kadota, Katsuyuki Miura, Tomonori Okamura, Akira Fujiyoshi, Takayo ...
    2013 Volume 20 Issue 10 Pages 755-766
    Published: October 25, 2013
    Released: October 28, 2013
    [Advance publication] Released: July 05, 2013
    JOURNALS FREE ACCESS
    Aim: To examine whether subclinical atherosclerosis of the carotid arteries is concordant with the categories in the 2012 atherosclerosis prevention guidelines proposed by the Japan Atherosclerosis Society (JAS guidelines 2012), which adopted the estimated 10-year absolute risk of coronary artery disease (CAD) death in the NIPPON DATA80 Risk Assessment Chart.
    Methods: Between 2006 and 2008, 868 Japanese men 40 to 74 years of age without a history of cardiovascular disease were randomly selected from Kusatsu City, Japan. The intima media thickness (IMT) and plaque number from the common to internal carotid arteries were investigated using ultrasonography. The absolute risk of CAD death was estimated based on the individual risk factor data, and the mean IMT and plaque number in Categories Ⅰ, Ⅱ and Ⅲ of the guidelines were examined.
    Results: The estimated 10-year absolute risk of CAD was directly related to the IMT (mean IMT (mean±SD) (mm) for a 10-year absolute risk of ≥2.0% and ≥5.0%: 0.88±0.18 and 0.95±0.19, respectively) and the plaque number. These results are compatible with the categories described by the guidelines (mean IMT (mean±SD) (mm) for Categories Ⅰ, Ⅱ, and Ⅲ: 0.70±0.11, 0.81±0.16 and 0.88±0.18, respectively; mean plaque number: 0.9, 2.1 and 3, respectively). These findings were similar for Category Ⅲ participants with or without DM and CKD.
    Conclusions: Subclinical atherosclerosis of the carotid arteries is concordant with the 10-year absolute risk of CAD and the categories in the JAS guidelines 2012.
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  • Morihiro Matsuda, Ritsu Tamura, Naoko Kishida, Takatsugu Segawa, Kotar ...
    2013 Volume 20 Issue 10 Pages 767-776
    Published: October 25, 2013
    Released: October 28, 2013
    [Advance publication] Released: June 13, 2013
    JOURNALS FREE ACCESS
    Aim: Multislice computed tomography coronary angiography (CTCA) can be used to detect coronary plaques that predict the risk of cardiovascular events. This study aimed to identify the risk factors associated with the extent of coronary plaques detected using CTCA and to determine the value of adiponectin measurement for identifying high-risk patients with multivessel coronary atherosclerosis.
    Methods: The study included 298 patients who underwent CTCA for coronary artery disease (CAD) screening between July 2008 and October 2011. We investigated the relationship between the extent of coronary atherosclerosis in terms of the number of diseased vessels and various risk factors, including the serum adiponectin level.
    Results: The adiponectin level was found to be significantly associated with multivessel coronary atherosclerosis in a univariate analysis (p=0.001). A multivariate analysis revealed the adiponectin level to also be significantly associated with multivessel coronary atherosclerosis (p=0.01), independent of other significant risk factors, including an advanced age, male gender, diabetes mellitus (DM) and hypertension (HT). A receiver operating characteristic curve analysis revealed that a combination of these factors significantly predicted multivessel coronary atherosclerosis (area under the curve, 0.73;95% confidence interval, 0.67-0.78). As the number of these factors increased, the proportion of patients with multivessel coronary atherosclerosis increased, while the proportion of patients with normal coronary arteries decreased (p<0.0001).
    Conclusions: A low adiponectin level combined with an advanced age, male gender, DM, and HT is independently and incrementally associated with multivessel coronary atherosclerosis. The number of factors may predict the extent of coronary atherosclerosis in patients without documented CAD.
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Case Report
  • Hiroyasu Yamamoto, Misa Onishi, Naoko Miyamoto, Ryosuke Oki, Hiroyasu ...
    2013 Volume 20 Issue 10 Pages 777-784
    Published: October 25, 2013
    Released: October 28, 2013
    [Advance publication] Released: July 08, 2013
    JOURNALS FREE ACCESS
    Aim: Lipoprotein lipase (LPL) deficiency is a rare autosomal recessive disorder characterized by severe hypertriglyceridemia. Similar clinical phenotypes have been reported with respect to defects in several LPL-associated proteins. However, it remains controversial whether severe hypertriglyceridemia itself is atherogenic. We herein present a case of LPL deficiency due to novel combined mutations of glycosylphosphatidylinositol (GPI)-anchored high-density lipoprotein (HDL)-binding protein 1 (GPIHBP1) in a patient with coronary artery disease (CAD).
    Patient: We evaluated a 54-year-old woman with severe hypertriglyceridemia and double vessel CAD. Although the LPL mass and activity in the postheparin plasma were extremely low, no mutations were detected in the LPL gene itself.
    Results: Genetic analyses revealed that the patient had double homozygous mutations at 41 bp (c.41G>T) and 202 bp (c.202 T>C) in the GPIHBP1 gene, resulting in C14F and C68R, respectively. Although the C14F/C68R GPIHBP1 exhibited a normal LPL-binding activity, the levels of mutant proteins were extremely reduced compared to those of the wild-type proteins in vitro.
    Conclusion: We found novel combined mutations of GPIHBP1 in a patient with hypertriglyceridemia and severe CAD. The present case provides important insight into the pathogenesis of severe hypertriglyceridemia associated with atherosclerosis.
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