O025 Exposure to secondhand smoke and risk of peripheral arterial disease in Southern Chinese...
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O024 Public knowledge of heart attack symptoms and prevalence of self reported cardiovascular risk factors in Ilorin, Nigeria Philip M. Kolo* 1 , James A. Ogunmodede 1 , Halima S. bello 2 , Maruf S. gbadamosi 2 , Bolade F. Deleojo 2 , Ibrahim A. Katibi 1 , ayodele B. Omotoso 1 1 Department of Medicine, University of Ilorin, Nigeria, UNIVERSITY OF ILORIN, NIGERIA, 2 Department of Medicine, University of Ilorin, Nigeria, UNIVERSITY OF ILORIN TEACHING HOSPITAL, NIGERIA, Ilorin, Nigeria Introduction: The level of public knowledge of cardinal symptoms of heart attack corre- lates with the speed the individuals seek medical attention if they experience heart attack. Early thrombolysis or reperfusion improves the outcome of patients with acute coronary syndromes. Objectives: This study aimed at evaluating knowledge of heart attack and prevalence of self reported cardiovascular diseases among public servants in Ilorin, Nigeria Methods: A pretested structured questionnaire designed for the purpose of this study was administered to study participants in Ilorin. Information on the ability of participants to identify chore symptom of heart attack such as chest pain or discomfort was obtained. Respondent perception of heart attack symptoms and actions to be taken if the individual or a close relative is affected by the condition were elicited Results: Six hundred and one subjects consisting of 312 (51.9%) males and 289 (48.1%) females were interviewed; and their mean age was 31.4 11.1 years. The mean age of the male participants was similar to that of the females (p¼0.7). Although, 78% of the re- spondents have heard about heart attack, only 44.4% could discriminate heart attack from other conditions. Similarly, knowledge of heart attack was higher in participants who were 40 years and older (48.3%) than those younger than 40 years (42.9%) of age. Higher proportion of women (50.2%) than men (39.1%) could identify a core symptom of heart attack. However, women reported higher prevalence of hypertension, diabetes, dyslipi- daemia, obesity, stroke and probable heart attacks than men. On the other hand, cigarette smoking was fourfold more common in males than females. Conclusion: There was low knowledge of heart attack symptoms among the participants studied. Women were more knowledgeable about symptoms of heart attack than males but the former reported a higher prevalence of cardiovascular diseases than the latter. There is need for public education on symptoms of the disease in Nigeria and importance of seeking urgent medical attention in affected persons. Disclosure of Interest: None Declared O025 Exposure to secondhand smoke and risk of peripheral arterial disease in Southern Chinese non-smokers: The Guangzhou Biobank Cohort Study-Cardiovascular Disease Subcohort Liya Lu* Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom Introduction: Active smoking is an established risk factor for peripheral arterial disease (PAD) but few studies have examined the association with secondhand smoke (SHS). Objectives: The aim of this study was to examine the association between SHS exposure and PAD among Chinese non-smokers. Methods: We conducted a cross-sectional study using baseline data from the Cardiovas- cular Disease Sub-cohort Study; a sub-group of the Guangzhou Biobank Cohort Study (GBCS-CVD). Guangzhou residents aged 50 years were recruited between 2003 and 2008. Baseline data collection included measurement of ankle brachial pressure index (ABPI) and self-reported smoking status and SHS exposure. Univariate and multivariate logistic regression analyses were used to analyse the association between SHS and PAD (defined as ABPI<0.9). Results: Of the 1,507 non-smokers, 24 (1.6%) had PAD. Exposure to SHS at home of 25 hours per week, was reported by 16.7% of individuals with PAD compared with only 3.8% of those without PAD (c 2 test, p¼0.016). After adjustment for potential confounders, exposure to 25 hours per week at home was still associated with PAD (adjusted OR 7.96, 95% CI 2.09-30.34, p¼0.002). There was suggestion of a linear dose relationship among those exposed at home. Conclusion: As with coronary heart disease and stroke, SHS exposure is an independent risk factor for PAD in China. Continued enforcement of smoke-free legislation is needed to protect the general public from exposure. Disclosure of Interest: None Declared O026 Cardiomyocytes Secreted Mir-378 Is An Essential Regulator of Cardiac Hypertrophy And Cardiac Fibrosis Under Pressure Overload Jie Yuan* 1 , Chaoneng Wu 1 , Yong Ye 1 , Zhiwen Ding 2 , Xiaoyi Zhang 1 , Gui Gong 1 , Yunzeng Zou 1,2 1 Shanghai Institute of Cardivascular Diseases, Zhongshan Hosptial, 2 Institutes of Biomedical Sciences, Fudan University, Shanghai, China Introduction: Recent studies showed that microRNAs play essential roles in cardiovascular diseases.We found that miR-378 has a high expression pattern in the heart. Its level was markedly down-regulated in pressure overload-induced hypertrophic heart but was increased in circulation. Objectives: We hypothesized that miR-378 would be a critical regulator inpressure overload-induced cardiac remodeling. Methods: To investigate its roles, we constructedcardiac remodeling models by TAC in C57B/L6 mice. Chemicallymodified oligonucleotides miRNA mimics (miR-378-Agomir) and inhibitors (miR-378-Antagomir) treatment started 24h after TAC by intravenous in- jections on two consecutive days (n¼8/group). After two-week acute pressure overload, we examined left ventricular (LV) remodeling. Results: Comparing to sham, TAC group exhibited significant (p<0.05): 1) hypertrophy (LVAWd 0.770.05 mm vs 0.990.04 mm and HW/BW 0.450.01 vs 0.640.06); 2) upregulation of fetal genes ANP, BNP and b-MHC; 3) 3-fold increase in fibrosis around blood vessels; 4) upregulation of protein col I, col III, MMP9. However, compared to TAC group, TAC-Agomir group had significant (p<0.05): 1) suppression of hypertrophy (LVAWd 0.800.07mm and HW/BW 0.570.01); 2) downregulation of fetal genes; 3) alleviation of fibrosis. In contrast, miR-378-Antagomirgroup caused sustained cardiac hypertrophyand fibrosis, associated with a reinduction of fetal gene expression and collagen generation. Moreover, we found that miR-378 was only expressed in car- diomyocytes but not in cardiac fibroblasts. In primary cultures of caridomyoctyes, over- expression of miR-378 by transfecting miR-378 mimics can effectively prevent mechanic stretch-stimulated fetal genes and p-ERK upregulation (p<0.05). Deficiency of miR-378 alone by inhibitors was sufficient to inducefetal genes expression. In cultured cardiac fi- broblasts, overexpression of miR-378 significantly suppressedcol I, col III, MMP9 levels induced by mechanic stretching (p<0.05). Furthermore, we observed increased level of miR-378 inthe supernatant of stretching cardiomyocytes (p<0.05). When culturingcardiac fibroblasts with the supernatant, induction of col I, col III, MMP9 by mechanic stretching was significantly inhibited (p<0.05). Conclusion: These findings reveal orchestrating regulatory roles for miR-378 in pressure- overload induced cardiac remodeling. It shows that miR-378 not only suppresses cardiac hypertrophy endogenously but also controls cardiac fibrosis by paracrine. Disclosure of Interest: J. Yuan Grant/research support from: National Natural Science Funds of China (Grant No. 81200185), C. Wu: None Declared, Y. Ye: None Declared, Z. Ding: None Declared, X. Zhang: None Declared, G. Gong: None Declared, Y. Zou: None Declared O027 Novel GATA4 Binding Proteins, RbAp48/46 Is a Key Regulator of Post- Transcriptional Modification of GATA4 during Cardiomyocyte Hypertrophy Yoichi Sunagawa* 1,2 , Yasufumi Katanasaka 1,2 , Hidetoshi Suzuki 1 , Hiromichi Wada 2 , Akira Shimatsu 3 , Koji Hasegawa 2 , Tatsuya Morimoto 1 1 Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, 2 Division of Translational Research, 3 Clinical Research Institute, Kyoto Medical Center, Kyoto, Japan Introduction: Cardiac hypertrophy is being recognized as a critical event during the development of heart failure. A zinc finger protein GATA4 associates an intrinsic histone acetyltransferase p300 and regulates myocardial transcriptional activities in response to hypertrophic stimuli. We previously have reported that Retinoblastoma protein (Rb)- associated protein 48 and 46 (RbAp48/46) are novel component of the p300/GATA4 complex and form a repressor complex with HDACs in cardiomyocytes. However, precise functional regulation by RbAp48/46 during hypertrophic responses is still unknown. Objectives: We investigate that RbAp48/46 regulate hypertrophic responses by modulating post-translational modification GATA4 in cardiomyocyte. Results: RbAp48/46 inhibited phenylephrine (PE)-induced hypertrophic responses such as acetylation of GATA4, activation of the ANF and ET-1 promoters, and increase in cell size. On the contrary, knockdown of RbAp48/46 by shRNA augmented such responses. Knockdown of HDAC1/2 augmented PE-induced hypertrophy and failed to inhibitory effects by RbAp48/46. GST pull down assay showed that RbAp48/46 interacted with N-terminal domain of GATA4, which was near its S105 phosphorylation site. IP-WB assay using HEK293T cells demonstrated that active form of MEK1 induced S105 phosphory- lation of GATA4, the dissociation of RbAp48/46 with GATA4, the increase of p300-induced GATA4-acetylation, and synergistic activation of ANF and ET-1 promoters with p300/ GATA4. S105A mutant of GATA4 reversed these changes. Stimulation of cardiomyocytes with PE induced S105 phosphorylation of GATA4, the dissociation of GATA4 with RbAp48/46 and HDAC1/2, and the decrease of RbAp48/46 recruitments onto the GATA element of the ANF promoter. Conversely, PD98059, a MEK1 inhibitor, treatment inhibited GATA4-phosphorylation and this dissociation. Conclusion: In this study, we demonstrate that phosphorylation of GATA4 has a critical role on the dissociation of GATA4/RbAp48/46/HDAC repressor complex, the formation of 300/GATA4 activator complex, and the increase of GATA4 acetylation and hypertrophic responses. These findings suggest that RbAp48/46 may regulate hypertrophic responses involved in modulating the posttranslational modification crosstalk of GATA4. Disclosure of Interest: None Declared O028 Role of Technology In Creating Rheumatic Heart Disease Awareness Among School-Going Children In Kenya Duncan M. Matheka* 1 , Mellany Murgor 2 , Edward Kibochi 2 , Steve Nigel 2 , Joseph Nderitu 2 , Gary Selnow 3 1 Department of Medical Physiology, 2 University of Nairobi, Nairobi, Kenya, 3 WiRED International, New York City, United States Introduction: Rheumatic heart disease (RHD) is the most common cardiovascular disease in Kenya and mainly affects school-going children. As a preventable disease, its incidence may be significantly reduced by educating the community on preventive measures. GHEART Vol 9/1S/2014 j March, 2014 j ORAL/2014 WCC Orals e7 ORAL ABSTRACTS
Transcript of O025 Exposure to secondhand smoke and risk of peripheral arterial disease in Southern Chinese...
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RACTS
O024
Public knowledge of heart attack symptoms and prevalence of self reportedcardiovascular risk factors in Ilorin, Nigeria
Philip M. Kolo*1, James A. Ogunmodede1, Halima S. bello2, Maruf S. gbadamosi2,Bolade F. Deleojo2, Ibrahim A. Katibi1, ayodele B. Omotoso11Department of Medicine, University of Ilorin, Nigeria, UNIVERSITY OF ILORIN, NIGERIA,2Department of Medicine, University of Ilorin, Nigeria, UNIVERSITY OF ILORIN TEACHINGHOSPITAL, NIGERIA, Ilorin, Nigeria
Introduction: The level of public knowledge of cardinal symptoms of heart attack corre-lates with the speed the individuals seek medical attention if they experience heart attack.Early thrombolysis or reperfusion improves the outcome of patients with acute coronarysyndromes.Objectives: This study aimed at evaluating knowledge of heart attack and prevalence of selfreported cardiovascular diseases among public servants in Ilorin, NigeriaMethods: A pretested structured questionnaire designed for the purpose of this study wasadministered to study participants in Ilorin. Information on the ability of participants toidentify chore symptom of heart attack such as chest pain or discomfort was obtained.Respondent perception of heart attack symptoms and actions to be taken if the individualor a close relative is affected by the condition were elicitedResults: Six hundred and one subjects consisting of 312 (51.9%) males and 289 (48.1%)females were interviewed; and their mean age was 31.4 �11.1 years. The mean age of themale participants was similar to that of the females (p¼0.7). Although, 78% of the re-spondents have heard about heart attack, only 44.4% could discriminate heart attack fromother conditions. Similarly, knowledge of heart attack was higher in participants who were40 years and older (48.3%) than those younger than 40 years (42.9%) of age. Higherproportion of women (50.2%) than men (39.1%) could identify a core symptom of heartattack. However, women reported higher prevalence of hypertension, diabetes, dyslipi-daemia, obesity, stroke and probable heart attacks than men. On the other hand, cigarettesmoking was fourfold more common in males than females.Conclusion: There was low knowledge of heart attack symptoms among the participantsstudied. Women were more knowledgeable about symptoms of heart attack than males butthe former reported a higher prevalence of cardiovascular diseases than the latter. There isneed for public education on symptoms of the disease in Nigeria and importance of seekingurgent medical attention in affected persons.Disclosure of Interest: None Declared
O025
Exposure to secondhand smoke and risk of peripheral arterial disease in SouthernChinese non-smokers: The Guangzhou Biobank Cohort Study-CardiovascularDisease Subcohort
Liya Lu*Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom
Introduction: Active smoking is an established risk factor for peripheral arterial disease(PAD) but few studies have examined the association with secondhand smoke (SHS).Objectives: The aim of this study was to examine the association between SHS exposureand PAD among Chinese non-smokers.Methods: We conducted a cross-sectional study using baseline data from the Cardiovas-cular Disease Sub-cohort Study; a sub-group of the Guangzhou Biobank Cohort Study(GBCS-CVD). Guangzhou residents aged �50 years were recruited between 2003 and2008. Baseline data collection included measurement of ankle brachial pressure index(ABPI) and self-reported smoking status and SHS exposure. Univariate and multivariatelogistic regression analyses were used to analyse the association between SHS and PAD(defined as ABPI<0.9).Results: Of the 1,507 non-smokers, 24 (1.6%) had PAD. Exposure to SHS at home of �25hours per week, was reported by 16.7% of individuals with PAD compared with only 3.8%of those without PAD (c2 test, p¼0.016). After adjustment for potential confounders,exposure to �25 hours per week at home was still associated with PAD (adjusted OR 7.96,95% CI 2.09-30.34, p¼0.002). There was suggestion of a linear dose relationship amongthose exposed at home.Conclusion: As with coronary heart disease and stroke, SHS exposure is an independentrisk factor for PAD in China. Continued enforcement of smoke-free legislation is needed toprotect the general public from exposure.Disclosure of Interest: None Declared
O026
Cardiomyocytes Secreted Mir-378 Is An Essential Regulator of Cardiac HypertrophyAnd Cardiac Fibrosis Under Pressure Overload
Jie Yuan*1, Chaoneng Wu1, Yong Ye1, Zhiwen Ding2, Xiaoyi Zhang1, Gui Gong1, Yunzeng Zou1,21Shanghai Institute of Cardivascular Diseases, Zhongshan Hosptial, 2Institutes of BiomedicalSciences, Fudan University, Shanghai, China
Introduction: Recent studies showed that microRNAs play essential roles in cardiovasculardiseases.We found that miR-378 has a high expression pattern in the heart. Its level wasmarkedly down-regulated in pressure overload-induced hypertrophic heart but wasincreased in circulation.Objectives: We hypothesized that miR-378 would be a critical regulator inpressureoverload-induced cardiac remodeling.
GHEART Vol 9/1S/2014 j March, 2014 j ORAL/2014 WCC Orals
Methods: To investigate its roles, we constructedcardiac remodeling models by TAC inC57B/L6 mice. Chemicallymodified oligonucleotides miRNA mimics (miR-378-Agomir)and inhibitors (miR-378-Antagomir) treatment started 24h after TAC by intravenous in-jections on two consecutive days (n¼8/group). After two-week acute pressure overload, weexamined left ventricular (LV) remodeling.Results: Comparing to sham, TAC group exhibited significant (p<0.05): 1) hypertrophy(LVAWd 0.77�0.05 mm vs 0.99�0.04 mm and HW/BW 0.45�0.01 vs 0.64�0.06); 2)upregulation of fetal genes ANP, BNP and b-MHC; 3) 3-fold increase in fibrosis aroundblood vessels; 4) upregulation of protein col I, col III, MMP9. However, compared to TACgroup, TAC-Agomir group had significant (p<0.05): 1) suppression of hypertrophy(LVAWd 0.80�0.07mm and HW/BW 0.57�0.01); 2) downregulation of fetal genes; 3)alleviation of fibrosis. In contrast, miR-378-Antagomirgroup caused sustained cardiachypertrophyand fibrosis, associated with a reinduction of fetal gene expression andcollagen generation. Moreover, we found that miR-378 was only expressed in car-diomyocytes but not in cardiac fibroblasts. In primary cultures of caridomyoctyes, over-expression of miR-378 by transfecting miR-378 mimics can effectively prevent mechanicstretch-stimulated fetal genes and p-ERK upregulation (p<0.05). Deficiency of miR-378alone by inhibitors was sufficient to inducefetal genes expression. In cultured cardiac fi-broblasts, overexpression of miR-378 significantly suppressedcol I, col III, MMP9 levelsinduced by mechanic stretching (p<0.05). Furthermore, we observed increased level ofmiR-378 inthe supernatant of stretching cardiomyocytes (p<0.05). When culturingcardiacfibroblasts with the supernatant, induction of col I, col III, MMP9 by mechanic stretchingwas significantly inhibited (p<0.05).Conclusion: These findings reveal orchestrating regulatory roles for miR-378 in pressure-overload induced cardiac remodeling. It shows that miR-378 not only suppresses cardiachypertrophy endogenously but also controls cardiac fibrosis by paracrine.Disclosure of Interest: J. Yuan Grant/research support from: National Natural ScienceFunds of China (Grant No. 81200185), C. Wu: None Declared, Y. Ye: None Declared, Z.Ding: None Declared, X. Zhang: None Declared, G. Gong: None Declared, Y. Zou: NoneDeclared
O027
Novel GATA4 Binding Proteins, RbAp48/46 Is a Key Regulator of Post-Transcriptional Modification of GATA4 during Cardiomyocyte Hypertrophy
Yoichi Sunagawa*1,2, Yasufumi Katanasaka1,2, Hidetoshi Suzuki1, Hiromichi Wada2,Akira Shimatsu3, Koji Hasegawa2, Tatsuya Morimoto11Division of Molecular Medicine, School of Pharmaceutical Sciences, University of Shizuoka,Shizuoka, 2Division of Translational Research, 3Clinical Research Institute, Kyoto MedicalCenter, Kyoto, Japan
Introduction: Cardiac hypertrophy is being recognized as a critical event during thedevelopment of heart failure. A zinc finger protein GATA4 associates an intrinsic histoneacetyltransferase p300 and regulates myocardial transcriptional activities in response tohypertrophic stimuli. We previously have reported that Retinoblastoma protein (Rb)-associated protein 48 and 46 (RbAp48/46) are novel component of the p300/GATA4complex and form a repressor complex with HDACs in cardiomyocytes. However, precisefunctional regulation by RbAp48/46 during hypertrophic responses is still unknown.Objectives:We investigate that RbAp48/46 regulate hypertrophic responses by modulatingpost-translational modification GATA4 in cardiomyocyte.Results: RbAp48/46 inhibited phenylephrine (PE)-induced hypertrophic responses such asacetylation of GATA4, activation of the ANF and ET-1 promoters, and increase in cell size.On the contrary, knockdown of RbAp48/46 by shRNA augmented such responses.Knockdown of HDAC1/2 augmented PE-induced hypertrophy and failed to inhibitoryeffects by RbAp48/46. GST pull down assay showed that RbAp48/46 interacted withN-terminal domain of GATA4, which was near its S105 phosphorylation site. IP-WB assayusing HEK293T cells demonstrated that active form of MEK1 induced S105 phosphory-lation of GATA4, the dissociation of RbAp48/46 with GATA4, the increase of p300-inducedGATA4-acetylation, and synergistic activation of ANF and ET-1 promoters with p300/GATA4. S105A mutant of GATA4 reversed these changes. Stimulation of cardiomyocyteswith PE induced S105 phosphorylation of GATA4, the dissociation of GATA4 withRbAp48/46 and HDAC1/2, and the decrease of RbAp48/46 recruitments onto the GATAelement of the ANF promoter. Conversely, PD98059, a MEK1 inhibitor, treatmentinhibited GATA4-phosphorylation and this dissociation.Conclusion: In this study, we demonstrate that phosphorylation of GATA4 has a criticalrole on the dissociation of GATA4/RbAp48/46/HDAC repressor complex, the formation of300/GATA4 activator complex, and the increase of GATA4 acetylation and hypertrophicresponses. These findings suggest that RbAp48/46 may regulate hypertrophic responsesinvolved in modulating the posttranslational modification crosstalk of GATA4.Disclosure of Interest: None Declared
O028
Role of Technology In Creating Rheumatic Heart Disease Awareness AmongSchool-Going Children In Kenya
Duncan M. Matheka*1, Mellany Murgor2, Edward Kibochi2, Steve Nigel2, Joseph Nderitu2,Gary Selnow3
1Department of Medical Physiology, 2University of Nairobi, Nairobi, Kenya, 3WiREDInternational, New York City, United States
Introduction: Rheumatic heart disease (RHD) is the most common cardiovascular diseasein Kenya and mainly affects school-going children. As a preventable disease, its incidencemay be significantly reduced by educating the community on preventive measures.
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