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739 GENDER DIFFERENCES IN THE DEVELOPMENT OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH EARLY SIGNS OF CEREBROVASCULAR INSUFFICIENCY
79th EAS Congress
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
(CVD) risk factor and stroke cases. Periodontal infections are a leading culprit, with studies reporting associations between periodontal disease and CVD, but this studies the periodontal diagnosis and coronary risk show substantial variations. This study aimed to analysed the different methods of periodontal diagnosis (Periodontal Screening and Recording − PSR and Community Periodontal Index of Treatment Needs − CPITN) and correlation with Framingham coronary risk and NIH stroke score. The result of 830 subjects shown strong and significant associations between periodontal diagnosis and coronary risk (r = 0.830) or stroke NIH score (r = 07.23). Evidence continues to support an association among periodontal infections, atherosclerosis and cerebrovascular disease in different periodontal diagnosis and coronary risk stratification methods. 739 GENDER DIFFERENCES IN THE DEVELOPMENT OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH EARLY SIGNS OF CEREBROVASCULAR INSUFFICIENCY V.A. Myasoedova1 , I.A. Sobenin2 , D.M. Merculova2 , T.V. Kirichenko1 , U.A. Merculov2 , A.N. Orekhov2 . 1 Institiute for Atherosclerosis Research, 2 Institute of General Pathology and Pathophysiology, Moscow, Russia Aim: Human atherosclerosis is associated with gender. According to European Atherosclerosis Agency statistics, both in Russia and in Europe the mortality from cardiovascular disease and stroke is significantly higher in men than in women. The aim of the study was to investigated the clinical significance of intima-medial thickness of common carotid artery (CCA IMT) as an indicator of the natural history of atherosclerosis, in respect of an early signs of neurological symptoms of cerebrovascular insufficiency in men and women. Methods: In a cross-sectional study were included 225 participants. The IMT of common carotid artery was messured. Clinical significance of ultrasound parameters of atherosclerosis was studied in relation to early neurologic symptoms characteristic for the insufficiency of cerebral blood flow. Results: In men, the analysis of the relationship of the integral indicator of neurological status with characteristics of carotid atherosclerosis showed a correlation with the CCA mean and max IMT (r = 0.291, p = 0.008 and r = 0.254, p = 0.021, respectively), but not with atherosclerotic plaques (p = 0.47). Women have an integral indicator of neurological status correlated with all used the quantitative characteristics of atherosclerosis (r = 0.251, p = 0.003; r = 0.261, p = 0.002 and r = 0.316, p < 0.001, respectively). Conclusions: A correlation between direct indices of atherosclerosis and indicators of neurological status was revealed. It was demonstrated that ultrasonic characteristics of carotid atherosclerosis have a high clinical impact on early manifestations of neurologic symptoms both in men and women. 740 PREVALENCE OF METABOLIC SYNDROME IN PATIENTS WITH OSTEOPOROSIS D. Agapakis, E. Alexiou, I. Floudaras, S. Maraslis, C. Chatziathanasiadou, M. Damianidou, S. Sereti, E. Satsoglou. General Hospital of Goumenissa, Goumenissa, Greece Background: Metabolic syndrome (MS) is a cluster of risk factors associated with cardiovascular disease morbidity in middle and old age. At around the same age group is quite frequent the presence of osteoporosis, a major cause of morbidity. Objective: The aim of our study was to determine the prevalence of MS in osteoporotic patients. Material and Methods: A total of 324 individuals, 218 female and 106 male, of mean age 67 years (47−78) participated to the study. The data were collected by questionnaire and laboratory findings in the context of preventive control in our region. Screening for low bone mass with quantitative ultrasonography (QUS) was applied and osteoporosis was confirmed by dual-energy x-ray absorptiometry (DXA) wherever was necessary. Results: Osteoporosis was found in 68 subjects (21%). There were 64 postmenopausal women of mean age 66.5 years and also 4 men who were receiving cortisol for several reasons. History of fractures was reported by 13 osteoporotic patients (19.1%). Prevalence of MS was 23.5% (14 women, 2 men). In the group of patients with osteoporotic fractures, hypertension and diabetes mellitus were the dominant disorders (84.6% and 61.5% respectively). Obesity was present in only 10.3% of osteoporotic patients. Also, there was significant difference in age (group with MS: mean age 68.7 years, without MS: 61.3 years, p < 0.05). Conclusions: Our study shows high prevalence of MS in patients with osteoporosis. Diabetes mellitus was quite frequent among patients with osteoporotic fractures. The coexistence of MS and osteoporosis may increase the overall morbidity.
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741 EFFECT OF CASPASE INHIBITOR AC-DEVD-CHO ON APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS INDUCED BY ARTESUNATE J. Zhang, H. Chen, G. Wang, T. Yin, Y. Teng, C. Tang. Key Laboratory of Biorheology and Technology (Chongqing University), Ministry of Education, Chongqing Engineering Laboratory in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China Background: Numerous studies have shown that the proliferation of vascular smooth muscle cells (VSMCs) play a key role in restenosis. Artesunate, commonly used in Traditional Chinese Medicine for treating cardiovascular disease and with a triterpenoid and a peroxide structure, controls the apoptosis of different types of cells. The purpose of this study is to investigate the effects of artesunate on the apoptosis of VSMCs and to determine its precise mechanism. Methods: The effects of different concentrations of artesunate on the proliferation of VSMCs were determined by methyl thiazolyl tetrazolium (MTT). The morph of the cells treated with or without Artesunate observed by transmission electron microscopy (TEM). Cell cycle and apoptosis rates were detected by Flow Cytometry. The activity of caspase-3 was detected by Western Blot. Results: Artesunate inhibited proliferation of VSMCs in a dose- and timedependent manner within the concentration range of 7.5–120 mg/ml, and the inhibition rate of Artesunate can be as high as 89.49% at a concentration of 120 mg/ml with 72 hours. Cellular ultrastructures showed typical apoptotic features. The apoptosis rate increases gradually as the concentration of artesunate increases. Compared with the control group, the higherconcentration group showed significant variability. Caspase-3 inhibitor AcDEVD-CHO can significantly decrease this induction. Artesunate can induce caspase-3 activity significantly in VSMCs, but this activation may be significantly inhibited by Ac-DEVD-CHO. Conclusions: The results suggested that artesunate can significantly inhibit the VSMCs proliferation and increase VSMCs apoptosis and caspase-3 apoptotic pathway is the main mechanism that Artesunate promote the apoptosis of VSMCs. 742 INHIBITORY EFFECTS OF SAPPAN LIGNUM EXTRACT ON VASCULAR RESTENOSIS IN THE RAT CAROTID ARTERY BALLOON INJURY MODEL G. Wang1 , G. Long1 , B. Ling1 , C. Wei2 , H. Chen1 , L. Wu1 , T. Yin1 , C. Tang1 . 1 Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education; Chongqing Engineering Laboratory in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China, 2 Biomedical Center, Chongqing Academy of Science and Technology, Chongqing, China Introduction: Recently, inhibition of inflammation has become a promising approach to prevent vascular restenosis. Sappan Lignum (SL), a commonly prescribed drug used in Traditional Chinese Medicine, exhibits anti-inflammation property. This study aims to determine the molecular mechanism underlying the inhibitory effect of SL extract on vascular restenosis. Methods and Results: Using a rat carotid artery balloon injury model, we demonstrated that the SL extract had significantly inhibitory effects on vascular restenosis. Immunohistochemistry showed that the expression of TNF-a and NF-úBp65 in vascular was markedly reduced with the treatment of SL extract, while the expression of PCNA was mostly unaffected. Colorimetric assay of methylene blue incorporation demonstrated that the proliferation of cultured vascular smooth muscle cells (VSMCs) was not inhibited by SL serum. We also found that the treatment of SL serum did not result in cell cycle arrest of cultured VSMCs by flow cytometry. However, we found that the TNF-a expression of SL serum treated VSMCs was significantly down-regulated by RT-PCR and Western Blot. Furthermore, electrophoretic mobility shift assay (EMSA) showed that NF-úB activation was markedly suppressed by SL extract considerably through decreasing NF-úB p65 translocation and DNA binding activity. Conclusions: These data suggested that SL suppressed vascular restenosis may not through inhibiting vascular cell proliferation, but via down regulating TNF-a expression and TNF-a-induced NF-úB activation. 743 THE IMPACT OF LOW DENSITY LIPOPROTEIN RECEPTOR (LDLR) GENE MUTATION ON INCIDENCE OF PREMATURE CARDIOVASCULAR DISEASE, IN FAMILIAL HYPERCHOLESTEROLEMIC PATIENTS V. Metaxa, C. Pitsavos, I. Skoumas, A. Miliou, E. Oikonomou, K. Masoura, C. Stefanadis. 1st Cardiology Clinic, Hippokrateio Hospital, University of Athens, Athens, Greece Introduction: Familial hypercholesterolemia (FH) is associated with high incidence of premature cardiovascular disease (CVD). Aim: To evaluate the impact of the most common LDLR gene mutations in Greece, on the incidence of premature CVD. Methods: We enrolled 115 patients (49 males), from 54 families, of whom 67 children aged 19.5±8.5 years and 49 parents aged 50±20 years, clinically
Atherosclerosis Supplements 12, no. 1 (2011) 13–184
(CVD) risk factor and stroke cases. Periodontal infections are a leading culprit, with studies reporting associations between periodontal disease and CVD, but this studies the periodontal diagnosis and coronary risk show substantial variations. This study aimed to analysed the different methods of periodontal diagnosis (Periodontal Screening and Recording − PSR and Community Periodontal Index of Treatment Needs − CPITN) and correlation with Framingham coronary risk and NIH stroke score. The result of 830 subjects shown strong and significant associations between periodontal diagnosis and coronary risk (r = 0.830) or stroke NIH score (r = 07.23). Evidence continues to support an association among periodontal infections, atherosclerosis and cerebrovascular disease in different periodontal diagnosis and coronary risk stratification methods. 739 GENDER DIFFERENCES IN THE DEVELOPMENT OF SUBCLINICAL ATHEROSCLEROSIS IN PATIENTS WITH EARLY SIGNS OF CEREBROVASCULAR INSUFFICIENCY V.A. Myasoedova1 , I.A. Sobenin2 , D.M. Merculova2 , T.V. Kirichenko1 , U.A. Merculov2 , A.N. Orekhov2 . 1 Institiute for Atherosclerosis Research, 2 Institute of General Pathology and Pathophysiology, Moscow, Russia Aim: Human atherosclerosis is associated with gender. According to European Atherosclerosis Agency statistics, both in Russia and in Europe the mortality from cardiovascular disease and stroke is significantly higher in men than in women. The aim of the study was to investigated the clinical significance of intima-medial thickness of common carotid artery (CCA IMT) as an indicator of the natural history of atherosclerosis, in respect of an early signs of neurological symptoms of cerebrovascular insufficiency in men and women. Methods: In a cross-sectional study were included 225 participants. The IMT of common carotid artery was messured. Clinical significance of ultrasound parameters of atherosclerosis was studied in relation to early neurologic symptoms characteristic for the insufficiency of cerebral blood flow. Results: In men, the analysis of the relationship of the integral indicator of neurological status with characteristics of carotid atherosclerosis showed a correlation with the CCA mean and max IMT (r = 0.291, p = 0.008 and r = 0.254, p = 0.021, respectively), but not with atherosclerotic plaques (p = 0.47). Women have an integral indicator of neurological status correlated with all used the quantitative characteristics of atherosclerosis (r = 0.251, p = 0.003; r = 0.261, p = 0.002 and r = 0.316, p < 0.001, respectively). Conclusions: A correlation between direct indices of atherosclerosis and indicators of neurological status was revealed. It was demonstrated that ultrasonic characteristics of carotid atherosclerosis have a high clinical impact on early manifestations of neurologic symptoms both in men and women. 740 PREVALENCE OF METABOLIC SYNDROME IN PATIENTS WITH OSTEOPOROSIS D. Agapakis, E. Alexiou, I. Floudaras, S. Maraslis, C. Chatziathanasiadou, M. Damianidou, S. Sereti, E. Satsoglou. General Hospital of Goumenissa, Goumenissa, Greece Background: Metabolic syndrome (MS) is a cluster of risk factors associated with cardiovascular disease morbidity in middle and old age. At around the same age group is quite frequent the presence of osteoporosis, a major cause of morbidity. Objective: The aim of our study was to determine the prevalence of MS in osteoporotic patients. Material and Methods: A total of 324 individuals, 218 female and 106 male, of mean age 67 years (47−78) participated to the study. The data were collected by questionnaire and laboratory findings in the context of preventive control in our region. Screening for low bone mass with quantitative ultrasonography (QUS) was applied and osteoporosis was confirmed by dual-energy x-ray absorptiometry (DXA) wherever was necessary. Results: Osteoporosis was found in 68 subjects (21%). There were 64 postmenopausal women of mean age 66.5 years and also 4 men who were receiving cortisol for several reasons. History of fractures was reported by 13 osteoporotic patients (19.1%). Prevalence of MS was 23.5% (14 women, 2 men). In the group of patients with osteoporotic fractures, hypertension and diabetes mellitus were the dominant disorders (84.6% and 61.5% respectively). Obesity was present in only 10.3% of osteoporotic patients. Also, there was significant difference in age (group with MS: mean age 68.7 years, without MS: 61.3 years, p < 0.05). Conclusions: Our study shows high prevalence of MS in patients with osteoporosis. Diabetes mellitus was quite frequent among patients with osteoporotic fractures. The coexistence of MS and osteoporosis may increase the overall morbidity.
155
741 EFFECT OF CASPASE INHIBITOR AC-DEVD-CHO ON APOPTOSIS OF VASCULAR SMOOTH MUSCLE CELLS INDUCED BY ARTESUNATE J. Zhang, H. Chen, G. Wang, T. Yin, Y. Teng, C. Tang. Key Laboratory of Biorheology and Technology (Chongqing University), Ministry of Education, Chongqing Engineering Laboratory in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China Background: Numerous studies have shown that the proliferation of vascular smooth muscle cells (VSMCs) play a key role in restenosis. Artesunate, commonly used in Traditional Chinese Medicine for treating cardiovascular disease and with a triterpenoid and a peroxide structure, controls the apoptosis of different types of cells. The purpose of this study is to investigate the effects of artesunate on the apoptosis of VSMCs and to determine its precise mechanism. Methods: The effects of different concentrations of artesunate on the proliferation of VSMCs were determined by methyl thiazolyl tetrazolium (MTT). The morph of the cells treated with or without Artesunate observed by transmission electron microscopy (TEM). Cell cycle and apoptosis rates were detected by Flow Cytometry. The activity of caspase-3 was detected by Western Blot. Results: Artesunate inhibited proliferation of VSMCs in a dose- and timedependent manner within the concentration range of 7.5–120 mg/ml, and the inhibition rate of Artesunate can be as high as 89.49% at a concentration of 120 mg/ml with 72 hours. Cellular ultrastructures showed typical apoptotic features. The apoptosis rate increases gradually as the concentration of artesunate increases. Compared with the control group, the higherconcentration group showed significant variability. Caspase-3 inhibitor AcDEVD-CHO can significantly decrease this induction. Artesunate can induce caspase-3 activity significantly in VSMCs, but this activation may be significantly inhibited by Ac-DEVD-CHO. Conclusions: The results suggested that artesunate can significantly inhibit the VSMCs proliferation and increase VSMCs apoptosis and caspase-3 apoptotic pathway is the main mechanism that Artesunate promote the apoptosis of VSMCs. 742 INHIBITORY EFFECTS OF SAPPAN LIGNUM EXTRACT ON VASCULAR RESTENOSIS IN THE RAT CAROTID ARTERY BALLOON INJURY MODEL G. Wang1 , G. Long1 , B. Ling1 , C. Wei2 , H. Chen1 , L. Wu1 , T. Yin1 , C. Tang1 . 1 Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education; Chongqing Engineering Laboratory in Vascular Implants, Bioengineering College of Chongqing University, Chongqing, China, 2 Biomedical Center, Chongqing Academy of Science and Technology, Chongqing, China Introduction: Recently, inhibition of inflammation has become a promising approach to prevent vascular restenosis. Sappan Lignum (SL), a commonly prescribed drug used in Traditional Chinese Medicine, exhibits anti-inflammation property. This study aims to determine the molecular mechanism underlying the inhibitory effect of SL extract on vascular restenosis. Methods and Results: Using a rat carotid artery balloon injury model, we demonstrated that the SL extract had significantly inhibitory effects on vascular restenosis. Immunohistochemistry showed that the expression of TNF-a and NF-úBp65 in vascular was markedly reduced with the treatment of SL extract, while the expression of PCNA was mostly unaffected. Colorimetric assay of methylene blue incorporation demonstrated that the proliferation of cultured vascular smooth muscle cells (VSMCs) was not inhibited by SL serum. We also found that the treatment of SL serum did not result in cell cycle arrest of cultured VSMCs by flow cytometry. However, we found that the TNF-a expression of SL serum treated VSMCs was significantly down-regulated by RT-PCR and Western Blot. Furthermore, electrophoretic mobility shift assay (EMSA) showed that NF-úB activation was markedly suppressed by SL extract considerably through decreasing NF-úB p65 translocation and DNA binding activity. Conclusions: These data suggested that SL suppressed vascular restenosis may not through inhibiting vascular cell proliferation, but via down regulating TNF-a expression and TNF-a-induced NF-úB activation. 743 THE IMPACT OF LOW DENSITY LIPOPROTEIN RECEPTOR (LDLR) GENE MUTATION ON INCIDENCE OF PREMATURE CARDIOVASCULAR DISEASE, IN FAMILIAL HYPERCHOLESTEROLEMIC PATIENTS V. Metaxa, C. Pitsavos, I. Skoumas, A. Miliou, E. Oikonomou, K. Masoura, C. Stefanadis. 1st Cardiology Clinic, Hippokrateio Hospital, University of Athens, Athens, Greece Introduction: Familial hypercholesterolemia (FH) is associated with high incidence of premature cardiovascular disease (CVD). Aim: To evaluate the impact of the most common LDLR gene mutations in Greece, on the incidence of premature CVD. Methods: We enrolled 115 patients (49 males), from 54 families, of whom 67 children aged 19.5±8.5 years and 49 parents aged 50±20 years, clinically