Investigating the platelet metabolic, AMPK-ACC signaling in Coronary Artery Disease

Platelets are central actors in atherosclerosis and atherothrombosis. Stimulation of the AMP-activated protein kinase (AMPK) leads to phosphorylation and inhibition of acetyl-CoA carboxylase (ACC), the first committed enzyme for the de novo fatty acids synthesis in cells, including platelets. Given the impact of atherogenic environment on platelets, we hypothesized that AMPK-ACC signaling is activated in coronary artery disease (CAD) patients. The ACCTHEROMA trial (NCT03034148) reveals platelet ACC phosphorylation (phosphoACC) as a promising marker for risk stratification in suspected CAD patients. It identifies high-risk patients and correlates with severity of coronary artery calcification. The triglycerides/high-density lipoprotein cholesterol ratio is strongly associated with increased phosphoACC, a metabolic signature of the platelet-atherogenic lipid interplay in CAD patients. Phosphorylation and inhibition of ACC impacts platelet lipid content by down-regulating triglyceride lipid species, which in turn may affect platelet functions.(MED - Sciences médicales) -- UCL, 201

Docteur, j’ai une douleur dans le thorax ?

La douleur thoracique est une plainte très fréquente en consultation de médecine générale. La décision de transfert du patient en milieu hospitalier repose sur la caractérisation de la douleur, les antécédents cardiovasculaires, la réalisation d'un électrocardiogramme et l'état hémodynamique du patient. Le diagnostic de syndrome coronarien aigü (SCA) reste le premier diagnostic à évoquer. Il requiert dans la plupart des cas la réalisation d’une coronarographie mais le délai dépendra du type de SCA. L'infarctus avec sus-décalage du segment ST (STEMI) nécessite un transfert rapide en salle d'urgence car le délai de prise en charge (le temps entre le diagnostic et l’ouverture de l’artère coronaire, idéalement de moins de 60 min) conditionne le pronostic du patient. Le patient avec un infarctus sans sus- décalage du segment ST bénéficiera d'une coronarographie dans un délai de 24 à 72 heures. La pierre angulaire du traitement pharmacologique repose sur les inhibiteurs plaquettaires (aspirine et inhibiteurs du récepteur P2Y12) qui seront en général maintenus pour une durée d'un an. Le rôle du médecin généraliste est aussi crucial pour assurer la continuité des soins après l'hospitalisation car ces patients sont à haut risque de récidive.[Doctor, I feel pain in my chest] In general practice, chest pain is a very common clinical complaint. The general practitioner’s decision to refer a patient to hospital is mainly based on chest pain characterization, patient's cardiovascular history, as well as electrocardiographic and hemodynamic changes. Acute coronary syndrome (ACS) remains the main diagnostic challenge. In this case, a coronary angiography must generally be performed, but the delay will depend on the type of ACS. ST-segment elevation myocardial infarction (STEMI) requires rapid transport to the emergency room, given that the time to reperfusion (time span from diagnosis to coronary reperfusion, ideally <60 min) determines the patient’s prognosis. Patients with non-ST segment infarction (NSTE-ACS) should undergo angiography within 24 to 72 hours. Platelet inhibitors (aspirin and P2Y12 receptor inhibitors) are the cornerstone of pharmacological treatment. They are generally administered over 1 year. Beyond initial diagnosis, the general practitioner also plays a crucial role in ensuring continuity of care following hospitalization, since these patients are at high risk of relapse

Greater Efficacy of Total Thyroidectomy versus Radioiodine Therapy on Hyperthyroidism and Thyroid-Stimulating Immunoglobulin Levels in Patients with Graves Disease Previously Treated with Antithyroid Drugs

Abstract Aims: We compared the effects of total thyroidectomy (TTx) and radioiodine (RAI) administration on the course of thyroid hormones and thyroid stimulating immunoglobulins (TSI) in patients with Graves’ disease. Methods: We retrospectively studied 80 patients initially treated with antithyroid drugs (ATD) and requiring either RAI (8.3 ± 1.7 mCi of 131I; n=40) or TTx (n=40) as second-line therapy. Results: The TTx and RAI groups were not different, except for larger goitre, higher FT3 and more frequent Graves’ orbitopathy (GO) at diagnosis in the surgery group (p<0.05). A persistent remission of hyperthyroidism was observed in 97% of operated patients vs. 73% of the RAI patients at 3 years (p<0.01). TTx was followed by a rapid and steady decrease in TSI during the first 9 months, while a surge of antibodies was observed during the first 6 months after RAI, followed by a slow decrease over the next 18 months. At the last visit, high TSI levels were still observed in 18 and 60% of patients in the surgery and RAI groups, respectively (p < 0.001). Conclusions: Total thyroidectomy is more efficient than radioiodine to induce a rapid and permanent correction of hyperthyroidism and TSI decrease in patients previously treated with ATD

Resheathing of self-expanding bioprosthesis: Impact on procedural results, clinical outcome and prosthetic valve durability after transcatheter aortic valve implantation.

BACKGROUND: New transcatheter aortic valves were recently developed, enabling to resheath and reposition the prosthesis. The aim of the present study was to investigate whether the resheath manoeuvre did not impair the outcome of patients and the bioprosthesis durability after transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: On the 346 consecutive patients (84 ± 7 yrs-old, mean STS 6.7 ± 5%) undergoing a transfemoral TAVI in our institution since January 2008, 170 patients were implanted using a self-expanding valve (SEV). Among those, 39 (Group 1) required resheathing to achieve a successful implantation, while 131 did not require it (Group 2, N = 131). A balloon-expanding valve (BEV) was used in 176 patients (Group 3). Baseline characteristics were similar between groups. Device success was 98%, the rate of in-hospital death was 2%, and the number of procedural complications was similarly low, with no significant difference between groups. The follow-up was complete in 337 of 338 patients undergoing a successful TAVI (781 patients-year). Kaplan-Meier analysis showed that overall survival was 80 ± 2% and 42 ± 3% at 1 and 5 years respectively, with no difference between groups. On multivariate analysis, acute kidney injury, post-dilatation, pulmonary hypertension, porcelain aorta and STS score, but not resheath, were independant predictors of death after TAVI. The annual event rate of structural valve deterioration was 0.6% patients-year, and similar between groups. CONCLUSIONS: Our study shows that SEV resheath did not impair the procedural results, the outcome of patients nor the valve durability at short term after TAVI

Dual antiplatelet therapy is associated with high α-tubulin acetylation in circulating platelets from coronary artery disease patients

Platelet inhibition is the main treatment strategy to prevent atherothrombotic complications after acute coronary syndrome or percutaneous coronary intervention. Despite dual antiplatelet therapy (DAPT) combining aspirin and a P2Y12 receptor inhibitor, high on-treatment platelet reactivity (HPR) persists in some patients due to poor response to treatment and is associated with ischemic risk. Tubulin acetylation has been pointed out as a hallmark of stable microtubules responsible for the discoid shape of resting platelets. However, the impact of antiplatelet treatments on this post-translational modification has never been studied. This study investigated whether tubulin acetylation differs according to antiplatelet therapy and on-treatment platelet reactivity. Platelets were isolated from arterial blood samples of 240 patients admitted for coronary angiography, and levels of α-tubulin acetylation on lysine 40 (α-tubulin K40 acetylation) were assessed by western blot. We show that platelet α-tubulin K40 acetylation was significantly increased in DAPT-treated patients. In addition, the proportion of patients with high levels of α-tubulin K40 acetylation was drastically reduced among DAPT-treated patients with HPR. Multivariate logistic regression confirmed that DAPT resulting in adequate platelet inhibition was strongly associated with elevated α-tubulin K40 acetylation. In conclusion, our study highlights the role of elevated platelet α-tubulin K40 acetylation as a marker of platelet inhibition in response to DAPT. Clinical trial registration: https://clinicaltrials.gov - NCT03034148

Oxidized low-density lipoprotein, in contrast to inflammatory cytokines, activates AMPK-ACC signaling in human platelets

Proteomic

Acetyl-coa carboxylase regulates platelet lipid content in coronary artery disease patients

Proteomic

Early thrombogenicity of coronary stents: comparison of bioresorbable polymer sirolimus-eluting and bare metal stents in an aortic rat model.

Although 1-month dual antiplatelet therapy (DAPT) in patients treated with bare metal stents (BMS) is well established, the optimal duration of DAPT after implantation of a drug-eluting stent (DES) is still a matter of debate. The safety of shortened DAPT is under investigation due to concern about the risk of stent thrombosis. Data on platelet activation and prothrombotic response in vivo following bioresorbable polymer sirolimus-eluting stent (BP-SES) implantation are scarce. The aim of our study was to compare the early thrombogenicity of BP-SES with that of BMS in an aortic rat model. Overall, 30 rats underwent stent implantation in the abdominal aorta: BMS (Pro-Kinetic Energy; N=15) and BP-SES (Ultimaster Tansei; N=15) were compared in terms of their early thrombogenicity. CD62P exposure at the platelet surface and fibrinogen binding at the integrin receptor were not different between BMS and BP-SES over time. The thrombus coverage of the scaffold (0 vs. 0.1%, P=0.84) was similarly low in both groups at Day 28; thrombotic deposits had totally disappeared at Day 84. The endothelial strut coverage was similarly high at 1 month (90 vs. 95%, P=0.64) and 3 months (87 vs. 97%, P=0.99) following BMS and BP-SES implantation, respectively. This study demonstrates the low early thrombogenicity of a BP-SES implanted in an aortic rat model, which did not differ from a BMS. These data could be helpful to support the safety of a shortened 1-month DAPT duration following BP-SES implantation in the human coronary artery