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Tenascin-C deficiency attenuates abdominal aortic aneurysm formation
Abstracts / Atherosclerosis 252 (2016) e1ee196
EAS16-0060, CVD RISK FACTORS. 7 T MRI REVEALS DIFFUSE IRON DEPOSITION IN PUTAMEN AND CAUDATE NUCLEUS IN CADASIL B. Muinjonov 1, E. Giyazitdinova 2. 1 Tashkent, Uzbekistan; Medical Academy, Neurology, Tashkent, Uzbekistan
2
Tashkent
Objectives: The aim of this study is to quantify diffuse iron deposition in patients with the hereditary small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: 25 NOTCH3 mutation carriers and 18 healthy controls were examined using high-resolution T2*- weighted imaging on a 7 T whole body MRI scanner. Susceptibility-weighted MRI scans were analysed for areas of signal loss and increased phase shift. Phase shift measurements in deep grey nuclei, cortex and subcortical white matter were compared between mutation carriers and controls. For confirmation, ex vivo brain specimens from another three patients with CADASIL were analysed for iron deposition using ex vivo MRI combined with iron histochemistry. Results: In vivo MRI showed areas of decreased signal intensity and increased phase shift in mutation carriers. Compared with healthy controls, mutation carriers had significantly higher phase shift in the putamen (p¼0.0002) and caudate nucleus (p¼0.006). Ex vivo MRI showed decreased signal intensity in the putamen and caudate nucleus in all specimens. Histochemistry confirmed the presence of iron deposition in these nuclei. Conclusions: This study demonstrates increased diffuse iron accumulation in the putamen and caudate nucleus in patients with the small vessel disease CADASIL. This supports the hypothesis that small vessel disease contributes to the process of increased iron accumulation in the general population.
EAS16-0755, CVD RISK FACTORS. TENASCIN-C DEFICIENCY ATTENUATES ABDOMINAL AORTIC ANEURYSM FORMATION A.K. Schaefer 1, F. Nagel 1, 2, P. Kaiser 1, D. Santer 1, 3, K. Trescher 1, 2, A. Kiss 1, B.K. Podesser 1, 2. 1 Medical University of Vienna, Department of €tsklinikum St. Po €lten, Biomedical Research, Vienna, Austria; 2 Universita €lten, Austria; 3 Herzzentrum Hietzing, Division of Cardiac Surgery, St. Po Division of Cardiovascular Surgery, Vienna, Austria Objectives: Tenascin-C (TNC) is a matricellular protein produced by vascular smooth muscle cells and fibroblasts in various remodeling processes. In numerous cardiovascular pathologies high TNC levels are associated with unfavorable outcomes. TNC production has also been found in abdominal aortic aneurysms (AAA). The aim of the study is to evaluate whether TNC deficiency could attenuate AAA formation. Methods: We compared male AJ TNC -/- and AJ wildtype (WT) mice. After laparotomy and preparation of the infrarenal aorta, AAA were induced by periaortal CaCl2 0,5M application for 15 minutes. In the sham-operated groups the same procedure was performed, however aortas were incubated with saline solution. The aortic diameter was measured before AAA induction and before organ harvesting after 3 and 10 weeks. The main parameter was the ratio of the diameters. Results: TNC knockout (KO) mice with AAA showed significantly lower diameter ratios than the wildtype group 3 weeks (TNC KO: 1.39±0.25, WT: 1.67±0.22 p<0.05) and 10 weeks (TNC KO: 1.51±0.47, WT: 1.98±0.55 p<0.05) after AAA induction. No significant changes in diameter ratios were found in sham groups (3 weeks: TNC KO: 0.92±0.08, WT: 0.96±0.22, n.s., 10 weeks: TNC KO: 1.05±0.16, WT: 0.94±0.10, n.s.). Additionally, the score of aortic wall elastin structure disruption was significantly lower in TNC KO than in WT mice 10 weeks after AAA induction (TNC KO: 3.32±1.15, WT: 4.25±0.75 p<0.05). Conclusions: In our study we found first evidence that TNC deficiency is associated with reduced AAA formation. To identify possible causal
e21
pathways immunohistological and molecular biological assessments will be conducted.
EAS16-0408, CVD RISK FACTORS. A CASE OF FATAL OBSTRUCTIVE SHOCK A. Almaghraby, Y. Saleh, B. Hammad, A. Samoka, M. Elbahey, M. Seleem. Faculty of Medicine, Cardiology, Alexandria, Egypt Objectives: Cardiac tumours and tumour thrombi can present in a way mimicking pulmonary embolism and can lead to fatal obstructive shock. Methods: A 31-year-old-male patient, a non-smoker with no cardiovascular risk factors, diagnosed with left ankle synovial cell sarcoma in 2010 and hence underwent localized excision successfully. The patient started complaining of dyspnea with less than daily effort 4 months prior to presentation that progressed to dyspnea at rest 1 week prior to presentation. On the day of presentation, he started developing dizziness on minimal effort that was closely related to cough and straining. His physical examination revealed a toxic look, cyanotic tinge of lips, pallor, blood pressure was 100/70 mmHg, heart rate was 100 bpm, respiratory rate was 26 cycle/minute , grade II clubbing was noted in all his limbs. Electrocardiogram revealed sinus tachycardia, laboratory workup was unremarkable and chest X-Ray revealed average cardiothoracic ratio with evident right lung apical mass. Results: Echocardiography showed a huge fleshy mass occupying the right ventricle and its outflow tract. The patient was planned for CT angiography for proper evaluation of the extent of his disease but unfortunately died. Pathological analysis revealed synovial cell sarcoma. Conclusions: Cardiac tumors represent a relatively rare, yet challenging diagnosis. Secondary tumors are seen more frequently than primary tumors. Most of primary cardiac tumors are benign in origin, with primary malignant tumors accounting for 25% of cases.
EAS16-0929, CVD RISK FACTORS. CARDIOVASCULAR RISK FACTORS IN WOMEN AND MEN A. Nikolova, M. Milanova. University Hospital Pirogov, Cardiology, Sofia, Bulgaria Objectives: The objective of our study is to compare the prevalence of cardiovascular risk factors in women and men. Methods: A prospective study, including 200 consecutive patients (110 female and 90 male), on mean age 53,5±10,1 (from 20 to 87) years. We analyzed anthropological and demographic data e age, physical activity, family history and presence of cardiovascular or other diseases, lifestyle, dyslipidemia, blood pressure and body-mass index (BMI). For the purpose of the study a questionnaire was designed and filled in by the patients. Results: Reduced physical activity was the leading cardiovascular risk factor in our female patients - 72,7%, followed by active smoking 49,10%, hypertension 41,80%, dyslipidemia - 39,1%. However, in our male patients it is unhealthy diet e 78,40%, followed by reduced physical activity 75,3%, hypertension 45,70%, active smoking 41,2% and dyslipidemia - 41,2%. Measurement of the anthropometric indicators showed that the mean weight for the female group was 77,04±15,8 kg, height 1,68 ± 0,09 m; estimated mean BMI was 27,3±4,9 and the waist cirumference - 93,7±15,9 cm. The one in the male group showed that the mean weigh was 89,53±16,69 kg, height 1,77±0,07m; estimated mean BMI was 28,55±4,89 and the waist cirumference 100,86±14,30cm. Most of our patients had a combination of 2 or 3 risk factors. Conclusions: Prevalence of cardiovascular risk factors among female and male patients in our study is high. Implementation of lifestyle changes e regular physical activity, weight reduction, cessation of smoking and diet is the key step for the non-medical prevention of cardiovascular complications in these patients.
EAS16-0060, CVD RISK FACTORS. 7 T MRI REVEALS DIFFUSE IRON DEPOSITION IN PUTAMEN AND CAUDATE NUCLEUS IN CADASIL B. Muinjonov 1, E. Giyazitdinova 2. 1 Tashkent, Uzbekistan; Medical Academy, Neurology, Tashkent, Uzbekistan
2
Tashkent
Objectives: The aim of this study is to quantify diffuse iron deposition in patients with the hereditary small vessel disease cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods: 25 NOTCH3 mutation carriers and 18 healthy controls were examined using high-resolution T2*- weighted imaging on a 7 T whole body MRI scanner. Susceptibility-weighted MRI scans were analysed for areas of signal loss and increased phase shift. Phase shift measurements in deep grey nuclei, cortex and subcortical white matter were compared between mutation carriers and controls. For confirmation, ex vivo brain specimens from another three patients with CADASIL were analysed for iron deposition using ex vivo MRI combined with iron histochemistry. Results: In vivo MRI showed areas of decreased signal intensity and increased phase shift in mutation carriers. Compared with healthy controls, mutation carriers had significantly higher phase shift in the putamen (p¼0.0002) and caudate nucleus (p¼0.006). Ex vivo MRI showed decreased signal intensity in the putamen and caudate nucleus in all specimens. Histochemistry confirmed the presence of iron deposition in these nuclei. Conclusions: This study demonstrates increased diffuse iron accumulation in the putamen and caudate nucleus in patients with the small vessel disease CADASIL. This supports the hypothesis that small vessel disease contributes to the process of increased iron accumulation in the general population.
EAS16-0755, CVD RISK FACTORS. TENASCIN-C DEFICIENCY ATTENUATES ABDOMINAL AORTIC ANEURYSM FORMATION A.K. Schaefer 1, F. Nagel 1, 2, P. Kaiser 1, D. Santer 1, 3, K. Trescher 1, 2, A. Kiss 1, B.K. Podesser 1, 2. 1 Medical University of Vienna, Department of €tsklinikum St. Po €lten, Biomedical Research, Vienna, Austria; 2 Universita €lten, Austria; 3 Herzzentrum Hietzing, Division of Cardiac Surgery, St. Po Division of Cardiovascular Surgery, Vienna, Austria Objectives: Tenascin-C (TNC) is a matricellular protein produced by vascular smooth muscle cells and fibroblasts in various remodeling processes. In numerous cardiovascular pathologies high TNC levels are associated with unfavorable outcomes. TNC production has also been found in abdominal aortic aneurysms (AAA). The aim of the study is to evaluate whether TNC deficiency could attenuate AAA formation. Methods: We compared male AJ TNC -/- and AJ wildtype (WT) mice. After laparotomy and preparation of the infrarenal aorta, AAA were induced by periaortal CaCl2 0,5M application for 15 minutes. In the sham-operated groups the same procedure was performed, however aortas were incubated with saline solution. The aortic diameter was measured before AAA induction and before organ harvesting after 3 and 10 weeks. The main parameter was the ratio of the diameters. Results: TNC knockout (KO) mice with AAA showed significantly lower diameter ratios than the wildtype group 3 weeks (TNC KO: 1.39±0.25, WT: 1.67±0.22 p<0.05) and 10 weeks (TNC KO: 1.51±0.47, WT: 1.98±0.55 p<0.05) after AAA induction. No significant changes in diameter ratios were found in sham groups (3 weeks: TNC KO: 0.92±0.08, WT: 0.96±0.22, n.s., 10 weeks: TNC KO: 1.05±0.16, WT: 0.94±0.10, n.s.). Additionally, the score of aortic wall elastin structure disruption was significantly lower in TNC KO than in WT mice 10 weeks after AAA induction (TNC KO: 3.32±1.15, WT: 4.25±0.75 p<0.05). Conclusions: In our study we found first evidence that TNC deficiency is associated with reduced AAA formation. To identify possible causal
e21
pathways immunohistological and molecular biological assessments will be conducted.
EAS16-0408, CVD RISK FACTORS. A CASE OF FATAL OBSTRUCTIVE SHOCK A. Almaghraby, Y. Saleh, B. Hammad, A. Samoka, M. Elbahey, M. Seleem. Faculty of Medicine, Cardiology, Alexandria, Egypt Objectives: Cardiac tumours and tumour thrombi can present in a way mimicking pulmonary embolism and can lead to fatal obstructive shock. Methods: A 31-year-old-male patient, a non-smoker with no cardiovascular risk factors, diagnosed with left ankle synovial cell sarcoma in 2010 and hence underwent localized excision successfully. The patient started complaining of dyspnea with less than daily effort 4 months prior to presentation that progressed to dyspnea at rest 1 week prior to presentation. On the day of presentation, he started developing dizziness on minimal effort that was closely related to cough and straining. His physical examination revealed a toxic look, cyanotic tinge of lips, pallor, blood pressure was 100/70 mmHg, heart rate was 100 bpm, respiratory rate was 26 cycle/minute , grade II clubbing was noted in all his limbs. Electrocardiogram revealed sinus tachycardia, laboratory workup was unremarkable and chest X-Ray revealed average cardiothoracic ratio with evident right lung apical mass. Results: Echocardiography showed a huge fleshy mass occupying the right ventricle and its outflow tract. The patient was planned for CT angiography for proper evaluation of the extent of his disease but unfortunately died. Pathological analysis revealed synovial cell sarcoma. Conclusions: Cardiac tumors represent a relatively rare, yet challenging diagnosis. Secondary tumors are seen more frequently than primary tumors. Most of primary cardiac tumors are benign in origin, with primary malignant tumors accounting for 25% of cases.
EAS16-0929, CVD RISK FACTORS. CARDIOVASCULAR RISK FACTORS IN WOMEN AND MEN A. Nikolova, M. Milanova. University Hospital Pirogov, Cardiology, Sofia, Bulgaria Objectives: The objective of our study is to compare the prevalence of cardiovascular risk factors in women and men. Methods: A prospective study, including 200 consecutive patients (110 female and 90 male), on mean age 53,5±10,1 (from 20 to 87) years. We analyzed anthropological and demographic data e age, physical activity, family history and presence of cardiovascular or other diseases, lifestyle, dyslipidemia, blood pressure and body-mass index (BMI). For the purpose of the study a questionnaire was designed and filled in by the patients. Results: Reduced physical activity was the leading cardiovascular risk factor in our female patients - 72,7%, followed by active smoking 49,10%, hypertension 41,80%, dyslipidemia - 39,1%. However, in our male patients it is unhealthy diet e 78,40%, followed by reduced physical activity 75,3%, hypertension 45,70%, active smoking 41,2% and dyslipidemia - 41,2%. Measurement of the anthropometric indicators showed that the mean weight for the female group was 77,04±15,8 kg, height 1,68 ± 0,09 m; estimated mean BMI was 27,3±4,9 and the waist cirumference - 93,7±15,9 cm. The one in the male group showed that the mean weigh was 89,53±16,69 kg, height 1,77±0,07m; estimated mean BMI was 28,55±4,89 and the waist cirumference 100,86±14,30cm. Most of our patients had a combination of 2 or 3 risk factors. Conclusions: Prevalence of cardiovascular risk factors among female and male patients in our study is high. Implementation of lifestyle changes e regular physical activity, weight reduction, cessation of smoking and diet is the key step for the non-medical prevention of cardiovascular complications in these patients.