caa a22 4500 606158308 CHVBK 20210128100618.0 cr unu---uuuuu 210128e20151201xx s 000 0 eng 10.1007/s10557-015-6626-1 doi (NATIONALLICENCE)springer-10.1007/s10557-015-6626-1 Adenylyl Cyclase 9 Polymorphisms Reveal Potential Link to HDL Function and Cardiovascular Events in Multiple Pathologies: Potential Implications in Sickle Cell Disease [Elektronische Daten] [Eric Niesor, Renée Benghozi, Philippe Amouyel, Keith Ferdinand, Gregory Schwartz] Adenylyl cyclase 9 (ADCY9) mediates β2-adrenoceptor (β2-AR) signalling. Both proteins are associated with caveolae, specialized cholesterol-rich membrane substructures. Apolipoprotein A1 (ApoA1), the major protein component of high-density lipoprotein (HDL), removes cholesterol from cell membrane and caveolae and may thereby influence β2-AR signalling, shown in vitro to be modulated by cholesterol. Patients with Sickle Cell Disease (SCD) typically have low HDL and ApoA1 levels. In patients, mainly of African origin, with SCD, β2-AR activation may trigger adhesion of red blood cells to endothelial cells, leading to vascular occlusive events. Moreover, ADCY9 polymorphism is associated with risk of stroke in SCD. In recent clinical trials, ADCY9 polymorphism was found to be a discriminant factor associated with the risk of cardiovascular (CV) events in Caucasian patients treated with the HDL-raising compound dalcetrapib. We hypothesize that these seemingly disparate observations share a common mechanism related to interaction of HDL/ApoA1 and ADCY9 on β2-AR signalling. This review also raises the importance of characterizing polymorphisms that determine the response to HDL-raising and -mimicking agents in the non-Caucasian population at high risk of CV diseases and suffering from SCD. This may facilitate personalized CV treatments. Springer Science+Business Media New York, 2015 Adenylyl cyclase 9 nationallicence β2-adrenergic receptor nationallicence High-density lipoprotein nationallicence Apolipoprotein A1 nationallicence Sickle cell disease nationallicence Malaria nationallicence Niesor Eric F.Hoffmann-La Roche Ltd, Basel, Switzerland aut Benghozi Renée F.Hoffmann-La Roche Ltd, Basel, Switzerland aut Amouyel Philippe University Hospital of Lille, Lille, France aut Ferdinand Keith Tulane University School of Medicine, New Orleans, USA aut Schwartz Gregory Denver Veterans Affairs Medical Center, Denver, USA aut Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/6(2015-12-01), 563-572 0920-3206 29:6<563 2015 29 10557 https://doi.org/10.1007/s10557-015-6626-1 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 review-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10557-015-6626-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Niesor Eric F.Hoffmann-La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Benghozi Renée F.Hoffmann-La Roche Ltd, Basel, Switzerland aut NATIONALLICENCE 700 1- Amouyel Philippe University Hospital of Lille, Lille, France aut NATIONALLICENCE 700 1- Ferdinand Keith Tulane University School of Medicine, New Orleans, USA aut NATIONALLICENCE 700 1- Schwartz Gregory Denver Veterans Affairs Medical Center, Denver, USA aut NATIONALLICENCE 773 0- Cardiovascular Drugs and Therapy Springer US; http://www.springer-ny.com 29/6(2015-12-01), 563-572 0920-3206 29:6<563 2015 29 10557