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Acute coronary artery disease in young adult population of less than 40 years old, clinical and angiographic characteristics
UntitledBook1.book Page 186 Monday, March 20, 2017 2:28 PM
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Archives of Cardiovascular Diseases Supplements (2017) 9, 185-186
stasis. We examined whether the translocon (TLC), an ER calcium leak channel independent of IP3R and RyR, might play a role in ischemia reperfusion injury. Purpose Cytoplasmic perturbation during I/R is the major cause of mitochondrial calcium overload and mPTP activation leading to cell death. In the present work, we proposed that modulation of the ER calcium stocks upstream mitochondrial calcium uptake, by focusing on ER calcium leak through the TLC, could be a valuable strategy. Methods Primary cardiomyocytes from C57/BL6J male mice were isolated by Langendorff technique, and calcium measurements were performed using fluorescent calcium probes. Mice were also used as an in vivo model for I/R, in order to evaluate the infarct size and further study the signaling pathways involved in cell death. Results Our results show that TLC is an active calcium leak channel on the ER membrane and its activation decreased infarct size by near 20%. This decrease was independent of other calcium stores and associated with a switch in cardiomyocytes mortality from deadly apoptosis/necrosis to adaptive autophagy. Conclusion The modulation of calcium leak through TLC independently from mitochondria and SR calcium homeostasis might be a new way to protect the heart against ischemia-reperfusion injury. The author hereby declares no conflict of interest
518 Acute coronary artery disease in young adult population of less than 40 years old, clinical and angiographic characteristics E. George*, J. Costa, D. Metz Cardiologie et pathologies vasculaires, CHU Robert Debré, Reims, France *Corresponding author: [email protected] Introduction Acute coronary artery disease in young adult population is rare but serious. Thus, this patient profile is specific. The aim of this study was to evaluate their characteristics in this particular population. Methods Demographic, clinical, biological, and angiographic datas were retrospectively analyzed in 24 young patients of less than 40 years old admitted for an acute coronary syndrom between January 2015 and July 2016 in a cardiological intensive care unit. Results Patient were 34.8 +/– 5.3 years old, 87.5% male sex, and 58.3% came from a rural area. Main parameters were smoking (75%), overweight (50%), with a mean body mass index of (26 kg/m2 +/– 1.09), cannabis consumption (29.2%), familial history of coronary disease (37.5%) and dyslipaemia (33.3%). Angiographic evaluation revealed a majority of monotroncular lesion (54.2%), especially of the anterior interventricular branch of the left coronary artery in 50% of cases, circumflex and right coronary both in (25%). Drug-eluting stents were implanted in 66.7% of cases, bare-metal stent in 29.2%. Mechanical support was used in 16.7% of cases. Global mortality rate was 16.7%. Biological analysis revealed an increase of the following inflammatory markers: leukocytes (mean of 14.4 +/– 1.6 Giga/ L), polynuclear neutrophils (9.9 +/– 1.4 Giga/L), and C-Reactive protein (mean of 15.5 +/– 6,3mg/L).
© Elsevier Masson SAS. All rights reserved.
Conclusions Acute coronary syndrome of young adult population appears to be more frequent in men from rural area, overweighed, smoking especially cannabis. Coronary lesions are mostly monotroncular, on the anterior interventricular branch of the left coronary artery. Inflammation seems to be associated with this acute cardiac event. The author hereby declares no conflict of interest
225 Endothelial microparticles from ACS patients induce premature endothelial cells ageing and thrombogenicity: Role of the Ang II/ ATIR/NADPH oxidase-mediated activation of MAPKs and PI3-kinase pathways M. Abbas (1-2), L. Jesel(3-1), C. Auger* (1), L. Amoura (1-2), N. Messas (3), G. Manin (3), C. Rumig (4), AJ. Leon-Gonzalez (1), T.P. Ribeiro (1), G. Silva (1), R. Abou-Merhi (5), E. Hamade (5), M. Hecker (4), Y. Georg (3), N. Chakfe (3), P. Ohlmann (3), VB. Schini-Kerth (1), F. Toti (1), O. Morel (1-3) (1) UMR CNRS 7213, université de Strasbourg, ILLKIRCH-GRAFFENSTADEN – (2) EA7293 Stress Vasculaire et Tissulaire en Transplantation, Faculté de Pharmacie, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg – (3) Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Fédération de Médecine Translationnelle de Strasbourg, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France – (4) Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Allemagne – (5) Faculté des Sciences I. Laboratoire Génomique et Santé, Plateforme de Recherche en Sciences et Technologies, Université Libanaise, Hadath, Liban *Corresponding author: [email protected] Microparticles (MPs) have emerged as a surrogate marker of endothelial injury and cardiovascular risk. This study examined the possibility that MPs detected at high concentrations during acute coronary syndrome (ACS), promote premature endothelial cells ageing and thrombogenicity. Exposure of young P1 endothelial cells to MPs isolated from ACS patients induced increased senescence-associated β-galactosidase activity (SA β-gal), oxidative stress, early phosphorylation of MAPKs and Akt, and up-regulation of p53, p21 and p16. The MPs-induced oxidative stress involved NADPH oxidase, cyclooxygenases (COX) and the mitochondrial respiration complex. Selective depletion of endothelial-derived MPs (EMPs) from plasma samples prevented the induction of senescence. Pro-senescent MPs from ACS patients also promoted endothelial cell thrombogenicity through tissue factor up-regulation, shedding of procoagulant MPs, eNOS down-regulation and blunting of the endothelial NO-mediated inhibition of platelet aggregation. They exhibited angiotensin-converting enzyme (ACE) activity and induced the up-regulation of AT1 receptors and ACE activity in young P1 endothelial cells. Losartan, an AT1 receptor antagonist prevented the MPs-induced premature endothelial senescence. EMPs from ACS patients induce premature endothelial senescence and thrombogenicity through angiotensin II-induced redox-sensitive activation of MAPKs and PI3-kinase/Akt. These data shed light on the importance of the inhibition of the angiotensin system in the prevention of MPs-induced premature endothelial senescence. The author hereby declares no conflict of interest
186
Archives of Cardiovascular Diseases Supplements (2017) 9, 185-186
stasis. We examined whether the translocon (TLC), an ER calcium leak channel independent of IP3R and RyR, might play a role in ischemia reperfusion injury. Purpose Cytoplasmic perturbation during I/R is the major cause of mitochondrial calcium overload and mPTP activation leading to cell death. In the present work, we proposed that modulation of the ER calcium stocks upstream mitochondrial calcium uptake, by focusing on ER calcium leak through the TLC, could be a valuable strategy. Methods Primary cardiomyocytes from C57/BL6J male mice were isolated by Langendorff technique, and calcium measurements were performed using fluorescent calcium probes. Mice were also used as an in vivo model for I/R, in order to evaluate the infarct size and further study the signaling pathways involved in cell death. Results Our results show that TLC is an active calcium leak channel on the ER membrane and its activation decreased infarct size by near 20%. This decrease was independent of other calcium stores and associated with a switch in cardiomyocytes mortality from deadly apoptosis/necrosis to adaptive autophagy. Conclusion The modulation of calcium leak through TLC independently from mitochondria and SR calcium homeostasis might be a new way to protect the heart against ischemia-reperfusion injury. The author hereby declares no conflict of interest
518 Acute coronary artery disease in young adult population of less than 40 years old, clinical and angiographic characteristics E. George*, J. Costa, D. Metz Cardiologie et pathologies vasculaires, CHU Robert Debré, Reims, France *Corresponding author: [email protected] Introduction Acute coronary artery disease in young adult population is rare but serious. Thus, this patient profile is specific. The aim of this study was to evaluate their characteristics in this particular population. Methods Demographic, clinical, biological, and angiographic datas were retrospectively analyzed in 24 young patients of less than 40 years old admitted for an acute coronary syndrom between January 2015 and July 2016 in a cardiological intensive care unit. Results Patient were 34.8 +/– 5.3 years old, 87.5% male sex, and 58.3% came from a rural area. Main parameters were smoking (75%), overweight (50%), with a mean body mass index of (26 kg/m2 +/– 1.09), cannabis consumption (29.2%), familial history of coronary disease (37.5%) and dyslipaemia (33.3%). Angiographic evaluation revealed a majority of monotroncular lesion (54.2%), especially of the anterior interventricular branch of the left coronary artery in 50% of cases, circumflex and right coronary both in (25%). Drug-eluting stents were implanted in 66.7% of cases, bare-metal stent in 29.2%. Mechanical support was used in 16.7% of cases. Global mortality rate was 16.7%. Biological analysis revealed an increase of the following inflammatory markers: leukocytes (mean of 14.4 +/– 1.6 Giga/ L), polynuclear neutrophils (9.9 +/– 1.4 Giga/L), and C-Reactive protein (mean of 15.5 +/– 6,3mg/L).
© Elsevier Masson SAS. All rights reserved.
Conclusions Acute coronary syndrome of young adult population appears to be more frequent in men from rural area, overweighed, smoking especially cannabis. Coronary lesions are mostly monotroncular, on the anterior interventricular branch of the left coronary artery. Inflammation seems to be associated with this acute cardiac event. The author hereby declares no conflict of interest
225 Endothelial microparticles from ACS patients induce premature endothelial cells ageing and thrombogenicity: Role of the Ang II/ ATIR/NADPH oxidase-mediated activation of MAPKs and PI3-kinase pathways M. Abbas (1-2), L. Jesel(3-1), C. Auger* (1), L. Amoura (1-2), N. Messas (3), G. Manin (3), C. Rumig (4), AJ. Leon-Gonzalez (1), T.P. Ribeiro (1), G. Silva (1), R. Abou-Merhi (5), E. Hamade (5), M. Hecker (4), Y. Georg (3), N. Chakfe (3), P. Ohlmann (3), VB. Schini-Kerth (1), F. Toti (1), O. Morel (1-3) (1) UMR CNRS 7213, université de Strasbourg, ILLKIRCH-GRAFFENSTADEN – (2) EA7293 Stress Vasculaire et Tissulaire en Transplantation, Faculté de Pharmacie, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg – (3) Pôle d’Activité Médico-Chirurgicale Cardio-Vasculaire, Fédération de Médecine Translationnelle de Strasbourg, Nouvel Hôpital Civil, Centre Hospitalier Universitaire, Strasbourg, France – (4) Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Allemagne – (5) Faculté des Sciences I. Laboratoire Génomique et Santé, Plateforme de Recherche en Sciences et Technologies, Université Libanaise, Hadath, Liban *Corresponding author: [email protected] Microparticles (MPs) have emerged as a surrogate marker of endothelial injury and cardiovascular risk. This study examined the possibility that MPs detected at high concentrations during acute coronary syndrome (ACS), promote premature endothelial cells ageing and thrombogenicity. Exposure of young P1 endothelial cells to MPs isolated from ACS patients induced increased senescence-associated β-galactosidase activity (SA β-gal), oxidative stress, early phosphorylation of MAPKs and Akt, and up-regulation of p53, p21 and p16. The MPs-induced oxidative stress involved NADPH oxidase, cyclooxygenases (COX) and the mitochondrial respiration complex. Selective depletion of endothelial-derived MPs (EMPs) from plasma samples prevented the induction of senescence. Pro-senescent MPs from ACS patients also promoted endothelial cell thrombogenicity through tissue factor up-regulation, shedding of procoagulant MPs, eNOS down-regulation and blunting of the endothelial NO-mediated inhibition of platelet aggregation. They exhibited angiotensin-converting enzyme (ACE) activity and induced the up-regulation of AT1 receptors and ACE activity in young P1 endothelial cells. Losartan, an AT1 receptor antagonist prevented the MPs-induced premature endothelial senescence. EMPs from ACS patients induce premature endothelial senescence and thrombogenicity through angiotensin II-induced redox-sensitive activation of MAPKs and PI3-kinase/Akt. These data shed light on the importance of the inhibition of the angiotensin system in the prevention of MPs-induced premature endothelial senescence. The author hereby declares no conflict of interest