- Email: [email protected]
W01.126 Risk factors for atherosclerosis in children with family history of premature coronary artery disease
Workshops W4 Cytokines, the adipocyte, and atherosclerosis used (EDTA-K3) for DNA extraction, polimerase chain reaction and electrophoresis in poliacrylamide (10%). Exon 6 polymorphism, on chromosome 8p22, was studied (N291S). Resuts: N291S vat-ianr was observed in 11.4% of FCHL subjects. Analysis of lipoproreins and apolipoproreins demonstrated an association with no-HDLc in FCHL. Patients with vat-ianr showed an increase in triglycerides, Apolipoprorein B, and VLDL, and a decrease in HDLc and Apolipoprorein A1. Conclusions: FCHL patients with LPL variant N291S showed an increase in parameters related with a disturbance in triglycerides-rich lipoproreins catabolism, suggesting that genetic defective can contribute ro FCHL phenorype. Supported by a grant fi'om rhe Insriruro de Salud Cat'los III, RCMN (C03/08) Madrid, Spain
RISK FACTORS FOR ATHEROSCLEROSIS IN CHILDREN WITH FAMILY HISTORY OF PREMATURE CORONARY ARTERY DISEASE
R. Suril da Naranjo, M. Mat'quaz, M. Bat'rios, F. Chamallo, M. Torras, C. Yepez, N. Harnandez. University of Carabobo, School of
Medicine-Pharmacology Department, Valencia, Carabobo, Venezuela Epidemiologic srudias suggasr that rhe amount of anrioxidanr vitamin E ingasrad in food is associated with lower risk of Coronat'y Arrary Disaasa (CAD) and Arharosclarosis. Objective: To avaluara vitamin E and lipids profila. Methodology: 50 childran whose patents had suffarad CAD befora leaching the age of 55 years (study group) in compatison with a control group of 46 children with healthy parents. A Venezuelan Ethical Committee of Scientific and Technological Investigations approved this protocol. Serum Vitamin E (Tocopherol) were determined by HPLC and lipids were assayed by colofimetric methods. These results showed no significant differences between groups for absolute values of vitamin E. However, when Vitamin E was srandat'dized for lipids, Total Cholesterol (TC) or TC + Triglycerides (TG), Vitamin E values were lower (p>0.05) in rhe study group than in rhe control group (Vitamin E/TC 3.48-t-1.52 mM/mM and Vitamin E/TC+TG 2.82-t-1.24 mM/mM) versus (Vitamin E/TC 4.60-t-2.10mM/mM and Vitamin E/TC+TG 3.83-t-1.67 mM/mM). Additionally, risk indexes for CAD were significantly higher (p<0.05) in rhe study group. Conclusions: The children with family history of premature CAD showed deficiencies of anrioxidanr Vitamin E and alteration in lipids profile. Hence, measut'emenrs of anrioxidanr vitamin E in children might help ro identify risk increased of CAD and arheroscleroric disease. Supported by CDCH-UC.
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POLYMORPHISM T-1131C (SNP3) OF APO AV GENE INCREASES TRIGLYCERIDE LEVELS IDEPENDENTLY OF THE PRESENCE OF INSULIN RESISTANCE
H. Vavarkova, D. Novotn , D. Kar sek, M. Bud kov , L. Slav k, M. Huryra, M. Halenka. University Hospital, 3rd Department of lnternal Medicine,
Department of Biochemistry, Departement of Nuclear Medicine, Olomouc, Czech Republic INtroduction: Apolipoprorein (APO) AV gena has been idanrifiad racanrly. Savaral papers provad that polymorphism T-1131C of APOAV gana affacrs rha lavals of triglycerides in savaral populations. As incraasad triglyceride lavals have often bean found within rha syndroma of insulin rasisrance (IR), the aim of the present study was ro dararmina wharhar rha ganorypes TC and CC of T-1131C polymorphism of APOAV gena, usually acompanied with incraasad triglycarida concantrarions, ara also associarad with manifestations of IR. Methods: Polymorphism of apo AV was derarminad in 225 parianrs (121 women and 104 man) of our Lipid Clinic, axaminad within rha screening of familias with familial combinad hyparlipidamia (FCH). Polymorphism of T-1131C was dararminad by rha marhod of PCR+RFLP. Basidas lipid spectrum, apoprorains AI, B and lipoprorain (a), wa followad-up also IR markars (fasting glycamia, insulin, HOMA indax, C-pepride), and other pat'amarars associarad with IR-inflammarory markars (hs-CRP, ICAM-1, VCAM-1) and thrombotic mat'kars (fibrinogan, vWF, r-PA and PAI-1). Results: Tha ganorypes TC and CC were found in 23.5% of rha group under study (n=53, rhe genorype CC only in 3 persons) and compat'ad with rha genorype TT, rhaft prasanca was associated with highar triglyceride
29
levels (median 1.93 vs 1.55, p=0.006). Fasting glycemia, insulin, Homa index and C-.pepride were without any difference even after age, BMI and waist adjustment. Conclusion: Minor allele of rhe T-1131C polymorfism of APOAV gene influences significantly rhe levels of triglycerides, probably independently of rhe presence of IR. Supported by rhe grant IGA MZ R NB/6563-3.
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W4 CYTOKINES, THE ADIPOCYTE, AND ATHEROSCLEROSIS
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Ramji
INCREASE IN SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR IN OBESE SUBJECTS: RELATIONSHIP WITH BODY FAT DISTRIBUTION
K. Takahashi, S. Miyazawa-Hoshimoro, H. Bujo, N. Hashimoro, Y. Sairo.
Chiba University Graduate School of Medicine, Chiba, Japan Vasculat" andorhelial growth factor (VEGF) is an important angiogenic factor raporred ro induca migration and prolifararion of andorhalial cells, anhanca vascular parrnaabiliry, and modulara rhrombogeniciry. Ir has bean implicarad in rha parhoganic naovascularizarion associarad with diabaric rarinoparhy and arharosclerosis. Ovarwaighr and rha distribution of body far ate both associarad with rha davalopmanr of cat'diovascular disaasas. Adiposa rissua has been leVaalad ro produce and sacrara some bioacriva molaculas, which may hava important rolas in rhe davalopmanr of arheroscleroric disaasa in obasiry. Hara, we invasrigarad rhe rola of far accumulation and irs affacr on VEGF lavals in humans and animals. In 38 ovarwaighr or obesa subjacrs (11 mala and 27 femala, body mass index (BMI) 27-48 kg/m2), serum lavals of VEGF were daracrad using enzyme-linkad immunosorbenr assay. Adiposa rissua distribution was assessed by using abdominal compurad romography ar umbilical lavals. In ganarically obese mice (rib/rib), serum lavals of VEGF were maasut'ad dut'ing rha davalopmanr of obasiry. Exprassion lavals of VEGF mRNA in subcuranaous and visceral adiposa rissuas wara also datarmined by ravarsa transcriprasa-polymarasa chain raacrion analysis. Serum VEGF lavals was posirivaly corralarad with BMI (r = 0.58, p<0.001) and visceral far araa (r = 0.32, p<0.05) bur nor with subcuranaous far at'aa in human subjacrs. Moraovar, subjacrs with viscaral far accumulation(visceral far araa >= 100 cm 2) axhibirad significantly highar sarum VEGF than BMI-marchad control (298 -4- 116 vs 178 -4- 113 pg/ml, p<0.05). In db/db mice, serum lavals of VEGF was posirivaly ralarad ro body waighr (r = 0.66, p<0.005). VEGF mRNA was daracrad in both types of adiposa rissua in db/db mice bur incraasad only in visceral far dut'ing rha davalopmanr of obesity. Thasa data suggasr that an anhancad explession of rhe VEGF gena in visceral far may incraasa serum lavals and may have a rola in rha davalopmanr of arharosclerosis in visceral obasiry.
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SIGNAL TRANSDUCTION PATHWAYS AND TRANSCRIPTIONAL CONTROL MECHANISMS INVOLVED IN THE CYTOKINE-MEDIATED REGULATION OF KEY GENES IN MACROPHAGES IMPLICATED IN FOAM CELL FORMATION AND ATHEROSCLEROSIS
D. Ramji, P. Foka, S. h'vina, T. Hughas, S. Rogars, N. Singh, K. Graanow, S. Evans, E. Harvay, S. All. Cardiff University, Cardiff, United Kingdom The transforrnation of macrophages into foam cells replesents a critical step in rhe parhogenesis of arherosclerosis. The products of several genes have been implicated in foam cell forrnarion and arherosclerosis. The action of cyrokines on rhe expression of such genes will make a maj or conU'iburion ro rhe initiation and rhe development of rhe disease. The put'pose of this study was ro investigate rhe mechanisms by which cyrokines modulate rhe expression of such key genes, including lipoprorein lipase (LPL), apolipoprorein E (apoE) and ATP-binding cassette transporrel~A1 (ABCA1). We show that macrophage LPL activity, mRNA levels and protein content ate all decleased in a time- and dose-dependenr manner in response ro interferongamma [IFN-gamma] and transforrning growth facror-bera [TGF-bera]. The action of IFN-gamma is mediated through a novel pathway that involves rhe activation of casein kinase 2, which triggers a decrease in rhe binding of rhe U'anscriprion factors Spl and Sp3 ro legularory sequences plesenr in rhe LPL gene. TGF-bera also inhibits LPL gene transcription through Spl and Sp3 bur requh'es rhe action of rhe c-Jun NH2-rerrninal kinase/sU'ess-acrivared
74th EAS Congress, 17-20 April 2004, Seville, Spain
iiiiii:".O.'iiiiiiiiiiiiiiii
RISK FACTORS FOR ATHEROSCLEROSIS IN CHILDREN WITH FAMILY HISTORY OF PREMATURE CORONARY ARTERY DISEASE
R. Suril da Naranjo, M. Mat'quaz, M. Bat'rios, F. Chamallo, M. Torras, C. Yepez, N. Harnandez. University of Carabobo, School of
Medicine-Pharmacology Department, Valencia, Carabobo, Venezuela Epidemiologic srudias suggasr that rhe amount of anrioxidanr vitamin E ingasrad in food is associated with lower risk of Coronat'y Arrary Disaasa (CAD) and Arharosclarosis. Objective: To avaluara vitamin E and lipids profila. Methodology: 50 childran whose patents had suffarad CAD befora leaching the age of 55 years (study group) in compatison with a control group of 46 children with healthy parents. A Venezuelan Ethical Committee of Scientific and Technological Investigations approved this protocol. Serum Vitamin E (Tocopherol) were determined by HPLC and lipids were assayed by colofimetric methods. These results showed no significant differences between groups for absolute values of vitamin E. However, when Vitamin E was srandat'dized for lipids, Total Cholesterol (TC) or TC + Triglycerides (TG), Vitamin E values were lower (p>0.05) in rhe study group than in rhe control group (Vitamin E/TC 3.48-t-1.52 mM/mM and Vitamin E/TC+TG 2.82-t-1.24 mM/mM) versus (Vitamin E/TC 4.60-t-2.10mM/mM and Vitamin E/TC+TG 3.83-t-1.67 mM/mM). Additionally, risk indexes for CAD were significantly higher (p<0.05) in rhe study group. Conclusions: The children with family history of premature CAD showed deficiencies of anrioxidanr Vitamin E and alteration in lipids profile. Hence, measut'emenrs of anrioxidanr vitamin E in children might help ro identify risk increased of CAD and arheroscleroric disease. Supported by CDCH-UC.
•
POLYMORPHISM T-1131C (SNP3) OF APO AV GENE INCREASES TRIGLYCERIDE LEVELS IDEPENDENTLY OF THE PRESENCE OF INSULIN RESISTANCE
H. Vavarkova, D. Novotn , D. Kar sek, M. Bud kov , L. Slav k, M. Huryra, M. Halenka. University Hospital, 3rd Department of lnternal Medicine,
Department of Biochemistry, Departement of Nuclear Medicine, Olomouc, Czech Republic INtroduction: Apolipoprorein (APO) AV gena has been idanrifiad racanrly. Savaral papers provad that polymorphism T-1131C of APOAV gana affacrs rha lavals of triglycerides in savaral populations. As incraasad triglyceride lavals have often bean found within rha syndroma of insulin rasisrance (IR), the aim of the present study was ro dararmina wharhar rha ganorypes TC and CC of T-1131C polymorphism of APOAV gena, usually acompanied with incraasad triglycarida concantrarions, ara also associarad with manifestations of IR. Methods: Polymorphism of apo AV was derarminad in 225 parianrs (121 women and 104 man) of our Lipid Clinic, axaminad within rha screening of familias with familial combinad hyparlipidamia (FCH). Polymorphism of T-1131C was dararminad by rha marhod of PCR+RFLP. Basidas lipid spectrum, apoprorains AI, B and lipoprorain (a), wa followad-up also IR markars (fasting glycamia, insulin, HOMA indax, C-pepride), and other pat'amarars associarad with IR-inflammarory markars (hs-CRP, ICAM-1, VCAM-1) and thrombotic mat'kars (fibrinogan, vWF, r-PA and PAI-1). Results: Tha ganorypes TC and CC were found in 23.5% of rha group under study (n=53, rhe genorype CC only in 3 persons) and compat'ad with rha genorype TT, rhaft prasanca was associated with highar triglyceride
29
levels (median 1.93 vs 1.55, p=0.006). Fasting glycemia, insulin, Homa index and C-.pepride were without any difference even after age, BMI and waist adjustment. Conclusion: Minor allele of rhe T-1131C polymorfism of APOAV gene influences significantly rhe levels of triglycerides, probably independently of rhe presence of IR. Supported by rhe grant IGA MZ R NB/6563-3.
iiiiiii iiiiiiiiiiiiiiii
W4 CYTOKINES, THE ADIPOCYTE, AND ATHEROSCLEROSIS
iiiiii:O.'iiiiiiiiiiiiiiii
~
~
Ramji
INCREASE IN SERUM VASCULAR ENDOTHELIAL GROWTH FACTOR IN OBESE SUBJECTS: RELATIONSHIP WITH BODY FAT DISTRIBUTION
K. Takahashi, S. Miyazawa-Hoshimoro, H. Bujo, N. Hashimoro, Y. Sairo.
Chiba University Graduate School of Medicine, Chiba, Japan Vasculat" andorhelial growth factor (VEGF) is an important angiogenic factor raporred ro induca migration and prolifararion of andorhalial cells, anhanca vascular parrnaabiliry, and modulara rhrombogeniciry. Ir has bean implicarad in rha parhoganic naovascularizarion associarad with diabaric rarinoparhy and arharosclerosis. Ovarwaighr and rha distribution of body far ate both associarad with rha davalopmanr of cat'diovascular disaasas. Adiposa rissua has been leVaalad ro produce and sacrara some bioacriva molaculas, which may hava important rolas in rhe davalopmanr of arheroscleroric disaasa in obasiry. Hara, we invasrigarad rhe rola of far accumulation and irs affacr on VEGF lavals in humans and animals. In 38 ovarwaighr or obesa subjacrs (11 mala and 27 femala, body mass index (BMI) 27-48 kg/m2), serum lavals of VEGF were daracrad using enzyme-linkad immunosorbenr assay. Adiposa rissua distribution was assessed by using abdominal compurad romography ar umbilical lavals. In ganarically obese mice (rib/rib), serum lavals of VEGF were maasut'ad dut'ing rha davalopmanr of obasiry. Exprassion lavals of VEGF mRNA in subcuranaous and visceral adiposa rissuas wara also datarmined by ravarsa transcriprasa-polymarasa chain raacrion analysis. Serum VEGF lavals was posirivaly corralarad with BMI (r = 0.58, p<0.001) and visceral far araa (r = 0.32, p<0.05) bur nor with subcuranaous far at'aa in human subjacrs. Moraovar, subjacrs with viscaral far accumulation(visceral far araa >= 100 cm 2) axhibirad significantly highar sarum VEGF than BMI-marchad control (298 -4- 116 vs 178 -4- 113 pg/ml, p<0.05). In db/db mice, serum lavals of VEGF was posirivaly ralarad ro body waighr (r = 0.66, p<0.005). VEGF mRNA was daracrad in both types of adiposa rissua in db/db mice bur incraasad only in visceral far dut'ing rha davalopmanr of obesity. Thasa data suggasr that an anhancad explession of rhe VEGF gena in visceral far may incraasa serum lavals and may have a rola in rha davalopmanr of arharosclerosis in visceral obasiry.
~
SIGNAL TRANSDUCTION PATHWAYS AND TRANSCRIPTIONAL CONTROL MECHANISMS INVOLVED IN THE CYTOKINE-MEDIATED REGULATION OF KEY GENES IN MACROPHAGES IMPLICATED IN FOAM CELL FORMATION AND ATHEROSCLEROSIS
D. Ramji, P. Foka, S. h'vina, T. Hughas, S. Rogars, N. Singh, K. Graanow, S. Evans, E. Harvay, S. All. Cardiff University, Cardiff, United Kingdom The transforrnation of macrophages into foam cells replesents a critical step in rhe parhogenesis of arherosclerosis. The products of several genes have been implicated in foam cell forrnarion and arherosclerosis. The action of cyrokines on rhe expression of such genes will make a maj or conU'iburion ro rhe initiation and rhe development of rhe disease. The put'pose of this study was ro investigate rhe mechanisms by which cyrokines modulate rhe expression of such key genes, including lipoprorein lipase (LPL), apolipoprorein E (apoE) and ATP-binding cassette transporrel~A1 (ABCA1). We show that macrophage LPL activity, mRNA levels and protein content ate all decleased in a time- and dose-dependenr manner in response ro interferongamma [IFN-gamma] and transforrning growth facror-bera [TGF-bera]. The action of IFN-gamma is mediated through a novel pathway that involves rhe activation of casein kinase 2, which triggers a decrease in rhe binding of rhe U'anscriprion factors Spl and Sp3 ro legularory sequences plesenr in rhe LPL gene. TGF-bera also inhibits LPL gene transcription through Spl and Sp3 bur requh'es rhe action of rhe c-Jun NH2-rerrninal kinase/sU'ess-acrivared
74th EAS Congress, 17-20 April 2004, Seville, Spain
iiiiii:".O.'iiiiiiiiiiiiiiii