Pub Date : 2020-04-01DOI: 10.1016/j.atherosclerosissup.2020.01.002
Ashraf Reda , Ahmed Shawky Elserafy , Elsayed Farag , Tamer Mostafa , Nabil Farag , Atef Elbahry , Osama Sanad , Ahmed Bendary , Ahmed Elkersh , Ihab Attia , Morad Beshay , Mohammed Selim , Hazem Khamis
{"title":"Egyptian Association of Vascular Biology and Atherosclerosis (EAVA) consensus on the usage of pro protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors","authors":"Ashraf Reda , Ahmed Shawky Elserafy , Elsayed Farag , Tamer Mostafa , Nabil Farag , Atef Elbahry , Osama Sanad , Ahmed Bendary , Ahmed Elkersh , Ihab Attia , Morad Beshay , Mohammed Selim , Hazem Khamis","doi":"10.1016/j.atherosclerosissup.2020.01.002","DOIUrl":"10.1016/j.atherosclerosissup.2020.01.002","url":null,"abstract":"","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2020.01.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49130640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2020-04-01DOI: 10.1016/j.atherosclerosissup.2020.01.004
Alaa M. Abou El Soud, Hanan M. Kamal, Ahmed Tageldein Abdellah, Ahmed H. Abdel Moniem
{"title":"Cardiovascular Predictors of Stroke in Patients with Sinus Rhythm Versus Patients with Atrial Fibrillation in Suez Canal University Hospital","authors":"Alaa M. Abou El Soud, Hanan M. Kamal, Ahmed Tageldein Abdellah, Ahmed H. Abdel Moniem","doi":"10.1016/j.atherosclerosissup.2020.01.004","DOIUrl":"10.1016/j.atherosclerosissup.2020.01.004","url":null,"abstract":"","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2020.01.004","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45745785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.1016/j.atherosclerosissup.2019.08.040
Roman N. Rodionov , Natalia Jarzebska , Alfred Schneider , Annett Rexin , Jan Sradnick , Silke Brilloff , Jens Martens-Lobenhoffer , Stefanie M. Bode-Böger , Vladimir Todorov , Christian Hugo , Norbert Weiss , Bernd Hohenstein
Background and aims
Cardiovascular disease is nowadays the major cause of mortality and morbidity worldwide. The risk of developing cardiovascular disease is significantly increased in patients with diabetic nephropathy. It has been suggested that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthases (NOS), may play an important role in the pathogenesis of diabetic nephropathy. ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase 1 (DDAH1). The goal of this study was to test the hypothesis that elevation of systemic ADMA levels by knocking out DDAH1 would exacerbate functional and structural glomerular abnormalities in a murine model of diabetic nephropathy.
Methods
Streptozotocin (STZ) was used to induce diabetes in adult DDAH1 knock-out and wild type mice. Healthy mice served as controls. Mice were sacrificed after 20 weeks of diabetes. Plasma ADMA levels were assessed by isotope-dilution tandem mass spectrometry and albumin by ELISA. Kidneys were used for FACS analysis and were also stained for markers of inflammation, cell proliferation, glomerular cells and cell matrix.
Results
STZ led to development of diabetes mellitus in all injected animals. Deficiency of DDAH1 led to a significant increase in plasma ADMA levels in healthy and diabetic mice. The diabetic state itself did not influence systemic ADMA levels. Diabetic mice of both genotypes developed albuminuria and had increased glomerulosclerosis index. There were no changes in desmin expression, glomerular cell proliferation rate, matrix expansion and expression of Mac-2 antigen in the diabetic mice of both genotypes as compared to the healthy ones.
Conclusions
In summary, STZ-induced diabetes led to the development of early features of diabetic nephropathy. Deficiency of DDAH1 and subsequent increase in systemic ADMA levels did not exacerbate these changes, indicating that ADMA is not the major mediator of diabetic nephropathy in this experiment model.
{"title":"ADMA elevation does not exacerbate development of diabetic nephropathy in mice with streptozotocin-induced diabetes mellitus","authors":"Roman N. Rodionov , Natalia Jarzebska , Alfred Schneider , Annett Rexin , Jan Sradnick , Silke Brilloff , Jens Martens-Lobenhoffer , Stefanie M. Bode-Böger , Vladimir Todorov , Christian Hugo , Norbert Weiss , Bernd Hohenstein","doi":"10.1016/j.atherosclerosissup.2019.08.040","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.040","url":null,"abstract":"<div><h3>Background and aims</h3><p>Cardiovascular disease is nowadays the major cause of mortality and morbidity worldwide. The risk of developing cardiovascular disease is significantly increased in patients with diabetic nephropathy. It has been suggested that asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthases (NOS), may play an important role in the pathogenesis of diabetic nephropathy. ADMA is mainly metabolized by dimethylarginine dimethylaminohydrolase 1 (DDAH1). The goal of this study was to test the hypothesis that elevation of systemic ADMA levels by knocking out DDAH1 would exacerbate functional and structural glomerular abnormalities in a murine model of diabetic nephropathy.</p></div><div><h3>Methods</h3><p>Streptozotocin (STZ) was used to induce diabetes in adult DDAH1 knock-out and wild type mice. Healthy mice served as controls. Mice were sacrificed after 20 weeks of diabetes. Plasma ADMA levels were assessed by isotope-dilution tandem mass spectrometry and albumin by ELISA. Kidneys were used for FACS analysis and were also stained for markers of inflammation, cell proliferation, glomerular cells and cell matrix.</p></div><div><h3>Results</h3><p>STZ led to development of diabetes mellitus in all injected animals. Deficiency of DDAH1 led to a significant increase in plasma ADMA levels in healthy and diabetic mice. The diabetic state itself did not influence systemic ADMA levels. Diabetic mice of both genotypes developed albuminuria and had increased glomerulosclerosis index. There were no changes in desmin expression, glomerular cell proliferation rate, matrix expansion and expression of Mac-2 antigen in the diabetic mice of both genotypes as compared to the healthy ones.</p></div><div><h3>Conclusions</h3><p>In summary, STZ-induced diabetes led to the development of early features of diabetic nephropathy. Deficiency of DDAH1 and subsequent increase in systemic ADMA levels did not exacerbate these changes, indicating that ADMA is not the major mediator of diabetic nephropathy in this experiment model.</p></div>","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78130712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
During pregnancy total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels increase significantly and lipoprotein apheresis (LA) is considered the most effective therapy in homozygous familial hypercholesterolaemia (HoFH) for modulating lipid and lipoprotein levels and reducing maternal and foetal complications.
Clinical case
A primigravida 28 years old Caucasian female patient, previously diagnosed as to be HoFH, was admitted at our outpatient service at the beginning of pregnancy.
Methods
The patient was continuously submitted to LA every two weeks without foetal complication. During pregnancy two methods have been utilised: selective apheresis, and later plasma exchange. At 33 weeks gestational age the patient developed progressively hypertension, associated to LDL-C levels increase. Weekly LA was favoured.
Results
At 34 weeks +5 days patient suddenly experienced acute chest pain and abnormal electrocardiogram heart tracing and cardiac enzymes increase.
An emergency caesarean section was performed without complications and the foetus was healthy. The patient was immediately transferred to Coronary Intensive Care Unit, where she was diagnosed non-ST elevation myocardial infarction (NSTEMI). Notwithstanding the patient improved in few days and was quickly discharged in fair clinical condition.
Conclusions
LA is a safe and effective tool in HoFH subjects even in pregnancy. Evidence based guidelines for the management of these patients during pregnancy are still lacking.
{"title":"A complicated pregnancy in homozygous familial hypercholesterolaemia treated with lipoprotein apheresis: A case report","authors":"Seila Perrone , Giuseppina Perrone , Roberto Brunelli , Serafina Di Giacomo , Paola Galoppi , Guendalina Flammini , Claudia Morozzi , Claudia Stefanutti","doi":"10.1016/j.atherosclerosissup.2019.08.033","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.033","url":null,"abstract":"<div><h3>Background and aims</h3><p>During pregnancy total cholesterol (TC) and low density lipoprotein<span><span> cholesterol (LDL-C) levels increase significantly and lipoprotein apheresis (LA) is considered the most effective therapy in homozygous </span>familial hypercholesterolaemia (HoFH) for modulating lipid and lipoprotein levels and reducing maternal and foetal complications.</span></p></div><div><h3>Clinical case</h3><p>A primigravida 28 years old Caucasian female patient, previously diagnosed as to be HoFH, was admitted at our outpatient service at the beginning of pregnancy.</p></div><div><h3>Methods</h3><p>The patient was continuously submitted to LA every two weeks without foetal complication. During pregnancy two methods have been utilised: selective apheresis, and later plasma exchange. At 33 weeks gestational age the patient developed progressively hypertension, associated to LDL-C levels increase. Weekly LA was favoured.</p></div><div><h3>Results</h3><p>At 34 weeks +5 days patient suddenly experienced acute chest pain and abnormal electrocardiogram heart tracing and cardiac enzymes increase.</p><p><span>An emergency caesarean section was performed without complications and the foetus was healthy. The patient was immediately transferred to Coronary </span>Intensive Care Unit, where she was diagnosed non-ST elevation myocardial infarction (NSTEMI). Notwithstanding the patient improved in few days and was quickly discharged in fair clinical condition.</p></div><div><h3>Conclusions</h3><p>LA is a safe and effective tool in HoFH subjects even in pregnancy. Evidence based guidelines for the management of these patients during pregnancy are still lacking.</p></div>","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86359403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5–10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD.
Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care.
Methods
Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure.
Results
Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy.
We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral.
Conclusions
Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially abo
{"title":"Lipoprotein apheresis in Germany – Still more commonly indicated than implemented. How can patients in need access therapy?","authors":"Franz Heigl , Tobias Pflederer , Reinhard Klingel , Reinhard Hettich , Norbert Lotz , Harduin Reeg , Volker J.J. Schettler , Eberhard Roeseler , Peter Grützmacher , Bernd Hohenstein , Ulrich Julius","doi":"10.1016/j.atherosclerosissup.2019.08.038","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.038","url":null,"abstract":"<div><h3>Background</h3><p><span>Although lipid-lowering drugs<span><span>, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol<span> (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5–10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. </span></span>In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of </span></span>lipoprotein<span> apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD.</span></p><p>Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care.</p></div><div><h3>Methods</h3><p>Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure.</p></div><div><h3>Results</h3><p>Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy.</p><p>We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral.</p></div><div><h3>Conclusions</h3><p>Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially abo","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89003267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.1016/j.atherosclerosissup.2019.08.023
Maciej Banach , Eric Bruckert , Olivier S. Descamps , Lars Ellegård , Marat Ezhov , Bernhard Föger , Zlatko Fras , Petri T. Kovanen , Gustavs Latkovskis , Winfried März , Demosthenes B. Panagiotakos , György Paragh , Daniel Pella , Angela Pirillo , Andrea Poli , Željko Reiner , Günter Silbernagel , Margus Viigimaa , Michal Vrablík , Alberico L. Catapano
{"title":"The role of red yeast rice (RYR) supplementation in plasma cholesterol control: A review and expert opinion","authors":"Maciej Banach , Eric Bruckert , Olivier S. Descamps , Lars Ellegård , Marat Ezhov , Bernhard Föger , Zlatko Fras , Petri T. Kovanen , Gustavs Latkovskis , Winfried März , Demosthenes B. Panagiotakos , György Paragh , Daniel Pella , Angela Pirillo , Andrea Poli , Željko Reiner , Günter Silbernagel , Margus Viigimaa , Michal Vrablík , Alberico L. Catapano","doi":"10.1016/j.atherosclerosissup.2019.08.023","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.023","url":null,"abstract":"","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89370619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.1016/j.atherosclerosissup.2019.08.041
Natalia Jarzebska , Sophia Georgi , Normund Jabs , Silke Brilloff , Renke Maas , Roman N. Rodionov , Christian Zietz , Sabrina Montresor , Bernd Hohenstein , Norbert Weiss
Background
The metabolic syndrome is a cluster of cardiovascular risk factors and is highly predictive for development of cardiovascular diseases. An association between elevated plasma levels of the endogenous inhibitor of nitric oxide synthases asymmetric dimethylarginine (ADMA) and risk of cardiovascular diseases has been demonstrated in numerous epidemiological studies. ADMA can be catabolized by dimethylarginine dimethylaminohydrolase (DDAH) or metabolized through a much less understood alternative pathway by alanine:glyoxylate aminotransferase 2 (AGXT2) with the formation of α-keto-δ-(N,N-dimethylguanidino)valeric acid (ADGV). Previous RT-PCR and Western Blot studies suggested that Agxt2 is expressed in the mouse kidney and liver at comparable levels, while Northern Blot and in-situ RNA-hybridisation experiments demonstrated that the kidney is the main organ of Agxt2 expression in rats. Given this discrepancy, the goal of the current study was to analyse the expression of AGXT2 in human tissues.
Material and methods
We analyzed AGXT2 expression in human tissues from a normal tissue bank by RT-PCR and further validated the results by Western Blot. We also performed immunohistochemical staining for AGXT2 and double fluorescent staining with an anti-AGXT2 antibody and a monoclonal anti-mitochondrial antibody.
Results
We saw the strongest expression of AGXT2 in the kidney and liver and confirmed this results on protein level. By IHC staining we were able to show that AGXT2 is present in the convoluted tubule in the kidney and in the liver hepatocytes. The double fluorescent staining revealed mitochondrial localization of AGXT2.
Conclusions
Our current data suggest that both hepatocytes and kidney tubular epithelial cells are the major sources of AGXT2 in humans. We also demonstrated the mitochondrial localization of human AGXT2 enzyme.
{"title":"Kidney and liver are the main organs of expression of a key metabolic enzyme alanine:glyoxylate aminotransferase 2 in humans","authors":"Natalia Jarzebska , Sophia Georgi , Normund Jabs , Silke Brilloff , Renke Maas , Roman N. Rodionov , Christian Zietz , Sabrina Montresor , Bernd Hohenstein , Norbert Weiss","doi":"10.1016/j.atherosclerosissup.2019.08.041","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.041","url":null,"abstract":"<div><h3>Background</h3><p><span><span><span>The metabolic syndrome is a cluster of cardiovascular risk factors and is highly predictive for development of cardiovascular diseases. An association between elevated plasma levels of the endogenous inhibitor of </span>nitric oxide synthases<span> asymmetric dimethylarginine (ADMA) and risk of cardiovascular diseases has been demonstrated in numerous epidemiological studies. ADMA can be catabolized by </span></span>dimethylarginine dimethylaminohydrolase<span> (DDAH) or metabolized through a much less understood alternative pathway by alanine:glyoxylate aminotransferase 2 (AGXT2) with the formation of α-keto-δ-(N,N-dimethylguanidino)valeric acid (ADGV). Previous RT-PCR and Western Blot studies suggested that </span></span><em>Agxt2</em> is expressed in the mouse kidney and liver at comparable levels, while Northern Blot and in-situ RNA-hybridisation experiments demonstrated that the kidney is the main organ of <em>Agxt2</em> expression in rats. Given this discrepancy, the goal of the current study was to analyse the expression of AGXT2 in human tissues.</p></div><div><h3>Material and methods</h3><p>We analyzed AGXT2 expression in human tissues from a normal tissue bank by RT-PCR and further validated the results by Western Blot. We also performed immunohistochemical staining for AGXT2 and double fluorescent staining with an anti-AGXT2 antibody and a monoclonal anti-mitochondrial antibody.</p></div><div><h3>Results</h3><p>We saw the strongest expression of <em>AGXT2</em> in the kidney and liver and confirmed this results on protein level. By IHC staining we were able to show that AGXT2 is present in the convoluted tubule in the kidney and in the liver hepatocytes. The double fluorescent staining revealed mitochondrial localization of AGXT2.</p></div><div><h3>Conclusions</h3><p>Our current data suggest that both hepatocytes and kidney tubular epithelial cells are the major sources of AGXT2 in humans. We also demonstrated the mitochondrial localization of human AGXT2 enzyme.</p></div>","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82217521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.1016/j.atherosclerosissup.2019.08.031
Claudia Stefanutti , Dario Mesce , Fernanda Pacella , Serafina Di Giacomo , Paolo Turchetti , Michele Forastiere , Edoardo Trovato Battagliola , Giuseppe La Torre , Gianpaolo Smaldone , Elena Pacella
Purpose
Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA).
Design
Observational study.
Subjects
To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)”, for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group).
Methods
Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA.
Main outcome measures
Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD).
Results
FH subjects had smaller RNFL superiorly (108 ± 19,38 μm OD/111 ± 16,56 μm OS FH-Group vs 127 ± 7,42 μm OD/129 ± 14,64 μm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ± 23,58 μm OD/115 ± 17,33 μm OS FH-Group vs 128 ± 18,15 μm OD/133 ± 17,38 μm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ± 12,94 μm OD/94 ± 10,49 μm OS FH-Group vs 101 ± 9,01 μm OD/101 ± 10,20 μm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ± 0,08 mm2 OD/0,33 ± 0,10 mm2 in OS FH-Group vs 0,21 ± 0,05 mm2 OD/0,21 ± 0,07 mm2 OS CT-Group; P < 0,001 OD; P = 0,002 OS).
Conclusions
Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA.
目的利用光学相干断层扫描(OCT)和光学相干断层扫描血管造影(OCTA)检测并量化家族性高胆固醇血症(FH)患者接受脂蛋白分离(LA)治疗后视网膜和脉络膜的形态功能改变。DesignObservational研究。待诊断的受试者:一组20名(40只眼睛)经临床和遗传学诊断为FH并正在接受治疗的患者(FH组),至少治疗2年,与对照组20名健康受试者(40只眼睛)进行比较,对照组血脂水平正常,无眼部疾病(ct组)。方法采用裂隙灯、双眼间接眼底镜、OCT和OCTA对患者进行观察。主要观察指标:最佳矫正视力(BVCA)、球面当量(SE)、眼内压(IOP)、黄斑中心厚度(CMT)、脉络膜厚度(CHT)、视网膜神经纤维层四个象限(RNFL (Superior = Sup;劣质 = 正无穷;鼻腔 = Nas颞 = Temp),以及四个象限的平均值(RNFL G)、中央凹无血管区(FAZ)和血管密度(VD)。ResultsFH受试者小RNFL优(108 ± 19日38 μm OD / 111 ± 16日56 vs 127μm OS FH-Group ± 7,42 μm OD / 129 ± 14日64 μm OS CT-Group;P & lt; 0001 OD和操作系统)和下级(108 ± 23日,58 μm OD / 115 ± 17日33 vs 128μm OS FH-Group ± 18日15 μm OD / 133 ± 17日,38 μm OS CT-Group;P = 0002 OD;P = 0001操作系统)。G RNFL因此较小(93 ± 12日94 μm OD / 94 ± 10,49 vs 101μm OS FH-Group ± 9日01 μm OD / 101 ± 10,20 μm OS CT-Group;03 OD P = 0;P = 0,02年OS)。跳频受试者更大的《法兰克福汇报》(0,31 ± 0,08年 平方毫米OD / 0, 33 ± 0,10 平方毫米OS FH-Group vs 0, 21 ± 0 05 平方毫米OD / 0, 21 ± 0,07年 平方毫米OS CT-Group;P & lt; 0001年 OD;P = 0002操作系统)。结论使用OCT和OCTA可以检测和量化FH患者视网膜血管损伤的早期征象。
{"title":"Optical coherence tomography of retinal and choroidal layers in patients with familial hypercholesterolaemia treated with lipoprotein apheresis","authors":"Claudia Stefanutti , Dario Mesce , Fernanda Pacella , Serafina Di Giacomo , Paolo Turchetti , Michele Forastiere , Edoardo Trovato Battagliola , Giuseppe La Torre , Gianpaolo Smaldone , Elena Pacella","doi":"10.1016/j.atherosclerosissup.2019.08.031","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.031","url":null,"abstract":"<div><h3>Purpose</h3><p>Detect and quantify morpho-functional alterations of the retina and choroid in patients affected by familial hypercholesterolemia (FH) treated with lipoprotein apheresis (LA) using optic coherence tomography (OCT) and optic coherence tomography-angriography (OCTA).</p></div><div><h3>Design</h3><p>Observational study.</p></div><div><h3>Subjects</h3><p>To be diagnosed: A group of 20 patients (40 eyes) being clinically and genetically diagnosed as FH and under treatment (FH-Group)”, for at least 2 years, was compared to a control group of 20 healthy subjects (40 eyes), with a normal lipid profile and no ocular disease (CT-Group).</p></div><div><h3>Methods</h3><p>Participants were studied with the slit lamp, binocular indirect fundoscopy, OCT and OCTA.</p></div><div><h3>Main outcome measures</h3><p>Best corrected visual acuity (BVCA), spherical equivalent (SE), intraocular pressure (IOP), central macular thickness (CMT), choroidal thickness (CHT), retinal nerve fiber layer in four quadrants (RNFL (Superior = Sup; Inferior = Inf; Nasal = Nas Temporal = Temp), and the mean value across the four quadrants (RNFL G), foveal avascular zone (FAZ) and vascular density (VD).</p></div><div><h3>Results</h3><p>FH subjects had smaller RNFL superiorly (108 ± 19,38 μm OD/111 ± 16,56 μm OS FH-Group vs 127 ± 7,42 μm OD/129 ± 14,64 μm OS CT-Group; P < 0,001 for both OD and OS) and inferiorly (108 ± 23,58 μm OD/115 ± 17,33 μm OS FH-Group vs 128 ± 18,15 μm OD/133 ± 17,38 μm OS CT-Group; P = 0,002 OD; P = 0,001 OS). G RNFL was consequently smaller (93 ± 12,94 μm OD/94 ± 10,49 μm OS FH-Group vs 101 ± 9,01 μm OD/101 ± 10,20 μm OS CT-Group; P = 0,03 OD; P = 0,02 OS). FH subjects had a larger FAZ (0,31 ± 0,08 mm<sup>2</sup> OD/0,33 ± 0,10 mm<sup>2</sup> in OS FH-Group vs 0,21 ± 0,05 mm<sup>2</sup> OD/0,21 ± 0,07 mm<sup>2</sup> OS CT-Group; P < 0,001 OD; P = 0,002 OS).</p></div><div><h3>Conclusions</h3><p>Early signs of retinal vessel damage in FH patients can be detected and quantified with OCT and OCTA.</p></div>","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78771415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-12-01DOI: 10.1016/j.atherosclerosissup.2019.08.044
Ulrike Schatz , Sabine Fischer , Gabriele Müller , Sergey Tselmin , Andreas L. Birkenfeld , Ulrich Julius , Winfried März , Stefan R. Bornstein
Objectives
Despite improved treatment, premature cardiovascular (CV) events remain a major health problem. Aim of this study was to evaluate the patterns of risk factors in patients with premature CV events.
Methods
CV risk factors (CVRF) were evaluated in 130 patients with a history of CV events (myocardial infarction, stroke, limb ischemia, stent and bypass intervention in any vessel bed) under 50 years of age attending our lipid clinic. Patients were also stratified according to their Lp(a) concentrations: group 1: 0–45 nmol/l (<18 mg/dl); group 2: >45–120 nmol/l (>18–50 mg/dl); group 3: >120 nmol/l (>50 mg/dl).
Results
The most common risk factors in our patients were male sex (75%), current (61%) and previous smoking (9%), arterial hypertension (70%), and a positive family history of early CV events (54%) and hyperlipidemia (69%). Only 27% had a BMI >30 kg/m2 and 14% had diabetes mellitus. 69% of patients with premature CV disease (CVD) showed Lp(a) levels > 120 nmol/l (>50 mg/dl). Patients with the highest Lp(a) showed a tendency of more frequent positive family histories of hyperlipidemia. They had experienced their first CV event on average 3 years earlier than those with low Lp(a). CV events predominantly involved coronary arteries. 85% of patients experienced at least one coronary event.
Conclusion
In patients with premature CV disease male sex, smoking, hypertension, a positive family history and elevated Lp(a) are the most important CV risk factors. Lp(a) should be considered in the management of young patients with CV disease.
{"title":"Cardiovascular risk factors in patients with premature cardiovascular events attending the University of Dresden Lipid Clinic","authors":"Ulrike Schatz , Sabine Fischer , Gabriele Müller , Sergey Tselmin , Andreas L. Birkenfeld , Ulrich Julius , Winfried März , Stefan R. Bornstein","doi":"10.1016/j.atherosclerosissup.2019.08.044","DOIUrl":"10.1016/j.atherosclerosissup.2019.08.044","url":null,"abstract":"<div><h3>Objectives</h3><p><span>Despite improved treatment, premature cardiovascular (CV) events remain a major </span>health problem<span>. Aim of this study was to evaluate the patterns of risk factors in patients with premature CV events.</span></p></div><div><h3>Methods</h3><p>CV risk factors (CVRF) were evaluated in 130 patients with a history of CV events (myocardial infarction, stroke, limb ischemia, stent and bypass intervention in any vessel bed) under 50 years of age attending our lipid clinic. Patients were also stratified according to their Lp(a) concentrations: group 1: 0–45 nmol/l (<18 mg/dl); group 2: >45–120 nmol/l (>18–50 mg/dl); group 3: >120 nmol/l (>50 mg/dl).</p></div><div><h3>Results</h3><p><span><span>The most common risk factors in our patients were male sex (75%), current (61%) and previous smoking (9%), arterial hypertension (70%), and a positive family history of early CV events (54%) and hyperlipidemia (69%). Only 27% had a </span>BMI >30 kg/m</span><sup>2</sup><span> and 14% had diabetes mellitus. 69% of patients with premature CV disease (CVD) showed Lp(a) levels > 120 nmol/l (>50 mg/dl). Patients with the highest Lp(a) showed a tendency of more frequent positive family histories of hyperlipidemia. They had experienced their first CV event on average 3 years earlier than those with low Lp(a). CV events predominantly involved coronary arteries. 85% of patients experienced at least one coronary event.</span></p></div><div><h3>Conclusion</h3><p>In patients with premature CV disease male sex, smoking, hypertension, a positive family history and elevated Lp(a) are the most important CV risk factors. Lp(a) should be considered in the management of young patients with CV disease.</p></div>","PeriodicalId":8592,"journal":{"name":"Atherosclerosis. Supplements","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.atherosclerosissup.2019.08.044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75069643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}