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Value of determining Lp(a) in health examinations
Thursday I3 October 1994: Poster Abstracts Lipoprotein(a) *Dept. of Health Science, Kobe Univ. Sch. of Med., Kusunoki-cho 7-5-1, Chuo-ku, Kobe 650, Japan
Plasma levels of Lp(a) strongly correlate with the incidence of coronary heart disease. However, the mechanism remains obscure. It has been reported that Lp(a) promotes proliferation of human smooth muscle cell more strongly than LDL (Grainger et al. Science 1993; 260: 1655-1658). Lp(a) binds to endothelial cells and inhibits cell-associated plasminogen activation and might modulate cell proliferation. We investigated the effect of Lp(a) on proliferation of human umbilical vein endothelial cells (HUVECs). We prepared Lp(a) by ultracentrifugation (d 1.05& 1.120 g/ml), followed by lysine-Sepharose chromatography. HUVECs were incubated with various concentrations of Lp(a) or LDL (9.38-15Oyg cholesterol/ml) in the presence of basic fibroblast growth factor (b-FGF) (1 ng/ml) and insulin (IO&ml). Both Lp(a) and LDL stimulated the growth of UVECs synergistically with b-FGF and insulin in a dose-dependent manner. The capacity of Lp(a) to stimulate cell proliferation was lower than that of LDL. Since b-FGF is considered to induce activation of latent TGF-/II by activating plasmin, we speculated that the lower mitogenic activity of Lp(a) was due to TGF-PI activation. AntiTGF$I neutralizing antibody promoted the proliferation of HUVECs by both Lp(a) and LDL to the same degree. Thus, TGF-/II was not involved in the difference of cell proliferation by Lp(a) and LDL, although the medium contained active TGF-PI. These resuhs suggest that a high concentration of Lp(a) could limit the healing response of the endothelium after injury. Value of determining Lp(a) in health examinations 1 Kobavw, Fukuo Y, Omura N, Fukushima M, Terashi A, Internal Medicine, Kosei General Hospital, 5-25-15 Yayoichou, Nakano-ku, Tokyo, Japan
Lp(a) was determined in subjects undergoing health examinations, and the significance of determining Lp(a) in such examinations was investigated by studying its relation to other risk factors for atherosclerosis. We studied 838 individuals. The mean Lp(a) value was 10.9 + 7.2 mg/dl. The Lp(a) value was significantly higher in the abnormal ECG group than in the normal ECG group. There were positive correlations with TC, B-Lp and LDL-C, and a significant negative correlation with TG. When the incidence of disease was compared by cut-off value, the incidence of abnormal ECGs was significantly higher at Lp(a) values of 25 mg/dI or higher. As Lp(a) showed positive correlations with TC, /3-Lp and LDL-C, the atherogenic risk of Lp(a) is evident. We suggest a cutoff value of 25 mg/dl for assessment of risk. These results indicate the significance of measuring Lp(a) in health examinations. Lipoprotein(a) localization in coronary atherosclerotic plaques is diierent in patients with stable angina from that in unstable angina and acute myocardial infarction I&J, Ueda M, Naruko T, Kasayuki N, Teragaki M, Takeuchi K, Takeda T, Kimura J, Yamamoto A, Becker AE, Isr Dept. of
281
plaque morphology (at the PTCA target site) was categorized as fibrous, atheromatous (lipid-rich with an attenuated fibrous cap) and intermediate (small lipid core and a thick fibrous cap). In SA, the pm-existent atherosclerotic plaque was either Iibrous (n = 1O)or intermediate (n = 15). In UA and AMI, the vast majority (21 of 22) were atheromatous. All atheromatous plaques contained marked depositions of Lp(a) in the fibrous cap, associated with abundant macrophages, T lymphocytes, but only a few smooth muscle cells. Plaques categorized as fibrous or intermediate showed only mild or moderate deposition of Lp(a) in the fibrous tissues and smooth muscle cells as the dominant cell type. The observations show that Lp(a) deposition relates to plaque morphology and may play a role in the susceptibility of plaques to rupture. Among plasma lipid components, Lp(a) is the most closely related to the impairment of vasoresponse to acetylcholine in patients with angiographically smooth coronary arteries Kawashima T, Yashiro A, Nakashima Y, Kuroiwa A, &u&h&
1
2nd Dept. of Int. Med, Univ. of Occupational and Environmental Health, Sch. of Med., Kitakyushu 807, Japan
This study was designed to examine whether Lp(a) levels are related to impaired vasoresponsiveness to acetylcholine in patients with angiographically smooth coronary arteries. In 24 patients with such arteries, 3Opg of acetylcholine was injected into the left main coronary after control angiography and the 8 diameter change was determined using a computer-assisted edgedetecting system. TC and TG, apolipoprotein and Lp(a) values were determined enzymatically, by a single-radial-immunodiffusion method and by ELISA respectively. The mean diameter (mean of segments 6, 8, 11 and 13) decreased by 12 + 17% from baseline in response to acetylcholine. The left anterior descending coronary artery (mean of segments 6 and 8) constricted more than the left circumflex coronary artery (mean of segments 11 and 13): mean diameter change -16 f 14% vs -1Of22%, P
1821
Itabashi, Tokyo, 173, Japan
Medicine, Osaka City Univ. Med. Sch., Abeno-ku, Osaka, Japan
The aim of this study was to determine whether Lp(a), consisting of ape(a) and LDL-like particles, is subject to structural alteration in human arterial intima and to define its possible contribution to atherogenesis. Mouse monoclonal antibody raised against chemically synthesized peptide of kringle 4-like domain of ape(a) was established, and designated as 161E2. By Western blot it was proved to react with ape(a) isolated free from LDL-like particles, but not with Lp(a), plasminogen, or LDL (Yamada et al 2nd fnt
I-5-7,
Asahi-machi,
Elevated plasma levels of Lp(a) am associated with coronary atherosclerosis. We studied the deposition of Lp(a) in atherosclerotic plaques in coronary arteries, used as target sites for PTCA, in patients who had died after the procedure, 20 patients had had stable angina (SA), 6 unstable angina (UA) and 16 acute myocardial infarction (AMI). Monoclonal antibodies were used against smooth muscle cells (HI-IF 35, CGA 7). macrophages (HAM 56). T lymphocytes (UCHL 1) and Lp(a) (lD1). The pre-existent
Conf on Lp(a), 1992).
By immunohistochemistry with 161E2 antibody, the ape(a) free from LDL-like particles was shown to accumulate in atherosclerotic lesions of unfixed, frozen sections of four coronary artery-atherectomy specimens and two routine biopsies from the ascending aorta performed during A-C bypass operation. Various
Atherosclerosis X, Montreal, October 1994
Plasma levels of Lp(a) strongly correlate with the incidence of coronary heart disease. However, the mechanism remains obscure. It has been reported that Lp(a) promotes proliferation of human smooth muscle cell more strongly than LDL (Grainger et al. Science 1993; 260: 1655-1658). Lp(a) binds to endothelial cells and inhibits cell-associated plasminogen activation and might modulate cell proliferation. We investigated the effect of Lp(a) on proliferation of human umbilical vein endothelial cells (HUVECs). We prepared Lp(a) by ultracentrifugation (d 1.05& 1.120 g/ml), followed by lysine-Sepharose chromatography. HUVECs were incubated with various concentrations of Lp(a) or LDL (9.38-15Oyg cholesterol/ml) in the presence of basic fibroblast growth factor (b-FGF) (1 ng/ml) and insulin (IO&ml). Both Lp(a) and LDL stimulated the growth of UVECs synergistically with b-FGF and insulin in a dose-dependent manner. The capacity of Lp(a) to stimulate cell proliferation was lower than that of LDL. Since b-FGF is considered to induce activation of latent TGF-/II by activating plasmin, we speculated that the lower mitogenic activity of Lp(a) was due to TGF-PI activation. AntiTGF$I neutralizing antibody promoted the proliferation of HUVECs by both Lp(a) and LDL to the same degree. Thus, TGF-/II was not involved in the difference of cell proliferation by Lp(a) and LDL, although the medium contained active TGF-PI. These resuhs suggest that a high concentration of Lp(a) could limit the healing response of the endothelium after injury. Value of determining Lp(a) in health examinations 1 Kobavw, Fukuo Y, Omura N, Fukushima M, Terashi A, Internal Medicine, Kosei General Hospital, 5-25-15 Yayoichou, Nakano-ku, Tokyo, Japan
Lp(a) was determined in subjects undergoing health examinations, and the significance of determining Lp(a) in such examinations was investigated by studying its relation to other risk factors for atherosclerosis. We studied 838 individuals. The mean Lp(a) value was 10.9 + 7.2 mg/dl. The Lp(a) value was significantly higher in the abnormal ECG group than in the normal ECG group. There were positive correlations with TC, B-Lp and LDL-C, and a significant negative correlation with TG. When the incidence of disease was compared by cut-off value, the incidence of abnormal ECGs was significantly higher at Lp(a) values of 25 mg/dI or higher. As Lp(a) showed positive correlations with TC, /3-Lp and LDL-C, the atherogenic risk of Lp(a) is evident. We suggest a cutoff value of 25 mg/dl for assessment of risk. These results indicate the significance of measuring Lp(a) in health examinations. Lipoprotein(a) localization in coronary atherosclerotic plaques is diierent in patients with stable angina from that in unstable angina and acute myocardial infarction I&J, Ueda M, Naruko T, Kasayuki N, Teragaki M, Takeuchi K, Takeda T, Kimura J, Yamamoto A, Becker AE, Isr Dept. of
281
plaque morphology (at the PTCA target site) was categorized as fibrous, atheromatous (lipid-rich with an attenuated fibrous cap) and intermediate (small lipid core and a thick fibrous cap). In SA, the pm-existent atherosclerotic plaque was either Iibrous (n = 1O)or intermediate (n = 15). In UA and AMI, the vast majority (21 of 22) were atheromatous. All atheromatous plaques contained marked depositions of Lp(a) in the fibrous cap, associated with abundant macrophages, T lymphocytes, but only a few smooth muscle cells. Plaques categorized as fibrous or intermediate showed only mild or moderate deposition of Lp(a) in the fibrous tissues and smooth muscle cells as the dominant cell type. The observations show that Lp(a) deposition relates to plaque morphology and may play a role in the susceptibility of plaques to rupture. Among plasma lipid components, Lp(a) is the most closely related to the impairment of vasoresponse to acetylcholine in patients with angiographically smooth coronary arteries Kawashima T, Yashiro A, Nakashima Y, Kuroiwa A, &u&h&
1
2nd Dept. of Int. Med, Univ. of Occupational and Environmental Health, Sch. of Med., Kitakyushu 807, Japan
This study was designed to examine whether Lp(a) levels are related to impaired vasoresponsiveness to acetylcholine in patients with angiographically smooth coronary arteries. In 24 patients with such arteries, 3Opg of acetylcholine was injected into the left main coronary after control angiography and the 8 diameter change was determined using a computer-assisted edgedetecting system. TC and TG, apolipoprotein and Lp(a) values were determined enzymatically, by a single-radial-immunodiffusion method and by ELISA respectively. The mean diameter (mean of segments 6, 8, 11 and 13) decreased by 12 + 17% from baseline in response to acetylcholine. The left anterior descending coronary artery (mean of segments 6 and 8) constricted more than the left circumflex coronary artery (mean of segments 11 and 13): mean diameter change -16 f 14% vs -1Of22%, P
1821
Itabashi, Tokyo, 173, Japan
Medicine, Osaka City Univ. Med. Sch., Abeno-ku, Osaka, Japan
The aim of this study was to determine whether Lp(a), consisting of ape(a) and LDL-like particles, is subject to structural alteration in human arterial intima and to define its possible contribution to atherogenesis. Mouse monoclonal antibody raised against chemically synthesized peptide of kringle 4-like domain of ape(a) was established, and designated as 161E2. By Western blot it was proved to react with ape(a) isolated free from LDL-like particles, but not with Lp(a), plasminogen, or LDL (Yamada et al 2nd fnt
I-5-7,
Asahi-machi,
Elevated plasma levels of Lp(a) am associated with coronary atherosclerosis. We studied the deposition of Lp(a) in atherosclerotic plaques in coronary arteries, used as target sites for PTCA, in patients who had died after the procedure, 20 patients had had stable angina (SA), 6 unstable angina (UA) and 16 acute myocardial infarction (AMI). Monoclonal antibodies were used against smooth muscle cells (HI-IF 35, CGA 7). macrophages (HAM 56). T lymphocytes (UCHL 1) and Lp(a) (lD1). The pre-existent
Conf on Lp(a), 1992).
By immunohistochemistry with 161E2 antibody, the ape(a) free from LDL-like particles was shown to accumulate in atherosclerotic lesions of unfixed, frozen sections of four coronary artery-atherectomy specimens and two routine biopsies from the ascending aorta performed during A-C bypass operation. Various
Atherosclerosis X, Montreal, October 1994