Skip to main content
Erschienen in: Cardiovascular Drugs and Therapy 5/2022

21.06.2021 | Original Article

Mirabegron Ameliorated Atherosclerosis of ApoE−/− Mice in Chronic Intermittent Hypoxia but Not in Normoxia

verfasst von: Yue Wang, Yue Wang, Hong-feng Jiang, Hai-ming Dang, Meng-ru Liu, Xin-yan Liu, Yang Yu, Jiang Xie, Xiao-jun Zhan, Hui-na Zhang, Xiao-fan Wu

Erschienen in: Cardiovascular Drugs and Therapy | Ausgabe 5/2022

Einloggen, um Zugang zu erhalten

Abstract

Purpose

It has been established that obstructive sleep apnea (OSA) is an independent risk factor for atherosclerosis. Chronic intermittent hypoxia (CIH) activates sympathoadrenal system and upregulates β3 adrenergic receptor (β3 AR). However, the effect of selective β3 AR agonist mirabegron in CIH-induced atherosclerosis remains unknown.

Methods

We generated a CIH-induced atherosclerosis model through exposing ApoE−/− mice to CIH (8 h per day, cyclic inspiratory oxygen fraction 5–21%, 60-s cycle) for 6 weeks after 4-week high-fat dieting and investigated the effects of mirabegron, a selective β3 AR agonist, on CIH-induced atherosclerosis. The coronary endarterectomy (CE) specimens from coronary artery disease patients with OSA and without OSA were collected.

Results

The expression of β3 AR was significantly elevated in CIH-induced atherosclerosis model. Furthermore, treatment with mirabegron (10mg/kg per day by oral administration for 6 weeks) ameliorated atherosclerosis in ApoE−/− mice in CIH but not in normoxia. Mechanistically, mirabegron activated β3 AR and ameliorated intraplaque oxidative stress by suppressing p22phox expression and reactive oxygen species (ROS) level. In addition, in human CE specimens, β3 AR was also upregulated associated with increased p22phox expression and ROS level both in the lumen and in the plaque of coronary artery in OSA subjects.

Conclusion

This study first demonstrated that mirabegron impeded the progression of CIH-induced atherosclerosis, at least in part, via β3 AR–mediated oxidative stress, suggesting a promising therapeutic strategy for protecting against atherosclerosis induced by CIH.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Chen X, He Y, Fu W, Sahebkar A, Tan Y, Xu S, et al. Histone deacetylases (HDACs) and atherosclerosis: a mechanistic and pharmacological review. Front Cell Dev Biol. 2020;8:581015.PubMedPubMedCentralCrossRef Chen X, He Y, Fu W, Sahebkar A, Tan Y, Xu S, et al. Histone deacetylases (HDACs) and atherosclerosis: a mechanistic and pharmacological review. Front Cell Dev Biol. 2020;8:581015.PubMedPubMedCentralCrossRef
2.
Zurück zum Zitat Jain T, Nikolopoulou EA, Xu Q, Qu A. Hypoxia inducible factor as a therapeutic target for atherosclerosis. Pharmacol Ther. 2018;183:22–33.PubMedCrossRef Jain T, Nikolopoulou EA, Xu Q, Qu A. Hypoxia inducible factor as a therapeutic target for atherosclerosis. Pharmacol Ther. 2018;183:22–33.PubMedCrossRef
3.
Zurück zum Zitat Remme WJ. The sympathetic nervous system and ischaemic heart disease. Eur Heart J. 1998;19:F62–71.PubMed Remme WJ. The sympathetic nervous system and ischaemic heart disease. Eur Heart J. 1998;19:F62–71.PubMed
4.
Zurück zum Zitat Berbée JF, Boon MR, Khedoe PP, et al. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat Commun. 2015;6:6356.PubMedCrossRef Berbée JF, Boon MR, Khedoe PP, et al. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development. Nat Commun. 2015;6:6356.PubMedCrossRef
5.
Zurück zum Zitat Gambardella J, Wang X, Mone P, Khondkar W, Santulli G. Genetics of adrenergic signaling drives coronary artery calcification. Atherosclerosis. 2020;310:88–90.PubMedPubMedCentralCrossRef Gambardella J, Wang X, Mone P, Khondkar W, Santulli G. Genetics of adrenergic signaling drives coronary artery calcification. Atherosclerosis. 2020;310:88–90.PubMedPubMedCentralCrossRef
6.
Zurück zum Zitat Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S, INCOSACT Initiative (International Collaboration of Sleep Apnea Cardiovascular Trialists). Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation. 2017;136:1840–50.PubMedPubMedCentralCrossRef Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S, INCOSACT Initiative (International Collaboration of Sleep Apnea Cardiovascular Trialists). Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation. 2017;136:1840–50.PubMedPubMedCentralCrossRef
7.
Zurück zum Zitat Ma L, Zhang J, Liu Y. Roles and mechanisms of obstructive sleep apnea-hypopnea syndrome and chronic intermittent hypoxia in atherosclerosis: evidence and prospective. Oxidative Med Cell Longev. 2016;8215082. Ma L, Zhang J, Liu Y. Roles and mechanisms of obstructive sleep apnea-hypopnea syndrome and chronic intermittent hypoxia in atherosclerosis: evidence and prospective. Oxidative Med Cell Longev. 2016;8215082.
8.
Zurück zum Zitat Bae S, Xiao Y, Li G, Casiano CA, Zhang L. Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart. Am J Physiol Heart Circ Physiol. 2003;285(3):H983–90.PubMedCrossRef Bae S, Xiao Y, Li G, Casiano CA, Zhang L. Effect of maternal chronic hypoxic exposure during gestation on apoptosis in fetal rat heart. Am J Physiol Heart Circ Physiol. 2003;285(3):H983–90.PubMedCrossRef
9.
Zurück zum Zitat Xu X, Lu WJ, Shi JY, Su YL, Liu YC, Wang L, et al. The gut microbial metabolite phenylacetylglycine protects against cardiac injury caused by ischemia/reperfusion through activating β2AR. Arch Biochem Biophys. 2021;697:108720.PubMedCrossRef Xu X, Lu WJ, Shi JY, Su YL, Liu YC, Wang L, et al. The gut microbial metabolite phenylacetylglycine protects against cardiac injury caused by ischemia/reperfusion through activating β2AR. Arch Biochem Biophys. 2021;697:108720.PubMedCrossRef
10.
11.
Zurück zum Zitat Nagai H, Kuwahira I, Schwenke DO, Tsuchimochi H, Nara A, Ogura S, et al. Pulmonary macrophages attenuate hypoxic pulmonary vasoconstriction via β3AR/iNOS pathway in rats exposed to chronic intermittent hypoxia. PLoS One. 2015;10:e0131923.PubMedPubMedCentralCrossRef Nagai H, Kuwahira I, Schwenke DO, Tsuchimochi H, Nara A, Ogura S, et al. Pulmonary macrophages attenuate hypoxic pulmonary vasoconstriction via β3AR/iNOS pathway in rats exposed to chronic intermittent hypoxia. PLoS One. 2015;10:e0131923.PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Vij M, Drake MJ. Clinical use of the beta3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome. Ther Adv Urol. 2015;7:241–8.PubMedPubMedCentralCrossRef Vij M, Drake MJ. Clinical use of the beta3 adrenoceptor agonist mirabegron in patients with overactive bladder syndrome. Ther Adv Urol. 2015;7:241–8.PubMedPubMedCentralCrossRef
13.
Zurück zum Zitat Bundgaard H, Axelsson A, Hartvig Thomsen J, Sørgaard M, Kofoed KF, Hasselbalch R, et al. The-first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail. 2017;19:566–75.PubMedCrossRef Bundgaard H, Axelsson A, Hartvig Thomsen J, Sørgaard M, Kofoed KF, Hasselbalch R, et al. The-first-in-man randomized trial of a beta3 adrenoceptor agonist in chronic heart failure: the BEAT-HF trial. Eur J Heart Fail. 2017;19:566–75.PubMedCrossRef
14.
Zurück zum Zitat Pouleur AC, Anker S, Brito D, Brosteanu O, Hasenclever D, Casadei B, et al. Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease beta3-left ventricular hypertrophy (Beta3-LVH). ESC Heart Fail. 2018;5(5):830–41.PubMedPubMedCentralCrossRef Pouleur AC, Anker S, Brito D, Brosteanu O, Hasenclever D, Casadei B, et al. Rationale and design of a multicentre, randomized, placebo-controlled trial of mirabegron, a beta3-adrenergic receptor agonist on left ventricular mass and diastolic function in patients with structural heart disease beta3-left ventricular hypertrophy (Beta3-LVH). ESC Heart Fail. 2018;5(5):830–41.PubMedPubMedCentralCrossRef
15.
Zurück zum Zitat García-Álvarez A, Pereda D, García-Lunar I, Sanz-Rosa D, Fernández-Jiménez R, García-Prieto J, et al. Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension. Basic Res Cardiol. 2016;111(4):49.PubMedPubMedCentralCrossRef García-Álvarez A, Pereda D, García-Lunar I, Sanz-Rosa D, Fernández-Jiménez R, García-Prieto J, et al. Beta-3 adrenergic agonists reduce pulmonary vascular resistance and improve right ventricular performance in a porcine model of chronic pulmonary hypertension. Basic Res Cardiol. 2016;111(4):49.PubMedPubMedCentralCrossRef
16.
Zurück zum Zitat Hadi T, Douhard R, Dias AMM, et al. Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPH oxidase activity and induces catalase expression via PPARγ activation. Biochim Biophys Acta. 1864;2017:1769–84. Hadi T, Douhard R, Dias AMM, et al. Beta3 adrenergic receptor stimulation in human macrophages inhibits NADPH oxidase activity and induces catalase expression via PPARγ activation. Biochim Biophys Acta. 1864;2017:1769–84.
17.
Zurück zum Zitat Mo W, Michel MC, Lee XW, Kaumann AJ, Molenaar P. The beta (3) -adrenoceptor agonist mirabegron increases human atrial force through beta (1) -adrenoceptors: an indirect mechanism? Br J Pharmacol. 2017;174(16):2706–15.PubMedPubMedCentralCrossRef Mo W, Michel MC, Lee XW, Kaumann AJ, Molenaar P. The beta (3) -adrenoceptor agonist mirabegron increases human atrial force through beta (1) -adrenoceptors: an indirect mechanism? Br J Pharmacol. 2017;174(16):2706–15.PubMedPubMedCentralCrossRef
18.
Zurück zum Zitat Korstanje C, Suzuki M, Yuno K, Sato S, Ukai M, Schneidkraut MJ, et al. Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron. J Pharmacol Toxicol Methods. 2017;87:74–81.PubMedCrossRef Korstanje C, Suzuki M, Yuno K, Sato S, Ukai M, Schneidkraut MJ, et al. Translational science approach for assessment of cardiovascular effects and proarrhythmogenic potential of the beta-3 adrenergic agonist mirabegron. J Pharmacol Toxicol Methods. 2017;87:74–81.PubMedCrossRef
19.
Zurück zum Zitat Poulain L, Thomas A, Rieusset J, Casteilla L, Levy P, Arnaud C, et al. Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J. 2014;43(2):513–22.PubMedCrossRef Poulain L, Thomas A, Rieusset J, Casteilla L, Levy P, Arnaud C, et al. Visceral white fat remodelling contributes to intermittent hypoxia-induced atherogenesis. Eur Respir J. 2014;43(2):513–22.PubMedCrossRef
20.
Zurück zum Zitat Sui W, Li H, Yang Y, Jing X, Xue F, Cheng J, et al. Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis. Proc Natl Acad Sci U S A. 2019;116:10937–42.PubMedPubMedCentralCrossRef Sui W, Li H, Yang Y, Jing X, Xue F, Cheng J, et al. Bladder drug mirabegron exacerbates atherosclerosis through activation of brown fat-mediated lipolysis. Proc Natl Acad Sci U S A. 2019;116:10937–42.PubMedPubMedCentralCrossRef
21.
Zurück zum Zitat Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2012;8:597–619.PubMedPubMedCentralCrossRef Berry RB, Budhiraja R, Gottlieb DJ, Gozal D, Iber C, Kapur VK, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine. J Clin Sleep Med. 2012;8:597–619.PubMedPubMedCentralCrossRef
22.
Zurück zum Zitat Binsalamah ZM, Al-Sarraf N, Chaturvedi RK, et al. Mid-term outcome and angiographic follow-up of endarterectomy of the left anterior descending artery in patients undergoing coronary artery bypass surgery. J Card Surg. 2014;29:1–7.PubMedCrossRef Binsalamah ZM, Al-Sarraf N, Chaturvedi RK, et al. Mid-term outcome and angiographic follow-up of endarterectomy of the left anterior descending artery in patients undergoing coronary artery bypass surgery. J Card Surg. 2014;29:1–7.PubMedCrossRef
23.
Zurück zum Zitat Wu QQ, Xiao Y, Duan MX, Yuan Y, Jiang XH, Yang Z, et al. Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades. Br J Pharmacol. 2018;175(9):1548–66.PubMedPubMedCentralCrossRef Wu QQ, Xiao Y, Duan MX, Yuan Y, Jiang XH, Yang Z, et al. Aucubin protects against pressure overload-induced cardiac remodelling via the β3 -adrenoceptor-neuronal NOS cascades. Br J Pharmacol. 2018;175(9):1548–66.PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Bruno G, Cencetti F, Pini A, Tondo A, Cuzzubbo D, Fontani F, et al. β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation. Oncogene. 2020;39(2):368–84.PubMedCrossRef Bruno G, Cencetti F, Pini A, Tondo A, Cuzzubbo D, Fontani F, et al. β3-adrenoreceptor blockade reduces tumor growth and increases neuronal differentiation in neuroblastoma via SK2/S1P2 modulation. Oncogene. 2020;39(2):368–84.PubMedCrossRef
25.
26.
Zurück zum Zitat Murayama H, Eguchi A, Nakamura M, Kawashima M, Nagahara R, Mizukami S, et al. Spironolactone in combination with α-glycosyl isoquercitrin prevents steatosis-related early hepatocarcinogenesis in rats through the observed NADPH oxidase modulation. Toxicol Pathol. 2018;46(5):530–9.PubMedCrossRef Murayama H, Eguchi A, Nakamura M, Kawashima M, Nagahara R, Mizukami S, et al. Spironolactone in combination with α-glycosyl isoquercitrin prevents steatosis-related early hepatocarcinogenesis in rats through the observed NADPH oxidase modulation. Toxicol Pathol. 2018;46(5):530–9.PubMedCrossRef
27.
Zurück zum Zitat Laouafa S, Ribon-Demars A, Marcouiller F, Roussel D, Bairam A, Pialoux V, et al. Estradiol protects against cardiorespiratory dysfunctions and oxidative stress in intermittent hypoxia. Sleep. 2017;40(8):1–13. Laouafa S, Ribon-Demars A, Marcouiller F, Roussel D, Bairam A, Pialoux V, et al. Estradiol protects against cardiorespiratory dysfunctions and oxidative stress in intermittent hypoxia. Sleep. 2017;40(8):1–13.
28.
Zurück zum Zitat Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med. 2007;175:1290–7.PubMedPubMedCentralCrossRef Savransky V, Nanayakkara A, Li J, Bevans S, Smith PL, Rodriguez A, et al. Chronic intermittent hypoxia induces atherosclerosis. Am J Respir Crit Care Med. 2007;175:1290–7.PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Song D, Fang G, Mao SZ, Ye X, Liu G, Miller EJ, et al. Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice. Atherosclerosis. 2018;270:68–75.PubMedCrossRef Song D, Fang G, Mao SZ, Ye X, Liu G, Miller EJ, et al. Selective inhibition of endothelial NF-κB signaling attenuates chronic intermittent hypoxia-induced atherosclerosis in mice. Atherosclerosis. 2018;270:68–75.PubMedCrossRef
30.
Zurück zum Zitat Phillips CL, Yee BJ, Marshall NS, Liu PY, Sullivan DR, Grunstein RR. Continuous positive airway pressure reduces postprandial lipidemia in obstructive sleep apnea: a randomized, placebo-controlled crossover trial. Am J Respir Crit Care Med. 2011;184:355–61.PubMedCrossRef Phillips CL, Yee BJ, Marshall NS, Liu PY, Sullivan DR, Grunstein RR. Continuous positive airway pressure reduces postprandial lipidemia in obstructive sleep apnea: a randomized, placebo-controlled crossover trial. Am J Respir Crit Care Med. 2011;184:355–61.PubMedCrossRef
31.
Zurück zum Zitat Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, et al. Impairment of endothelium- dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000;102:2607–10.PubMedCrossRef Kato M, Roberts-Thomson P, Phillips BG, Haynes WG, Winnicki M, Accurso V, et al. Impairment of endothelium- dependent vasodilation of resistance vessels in patients with obstructive sleep apnea. Circulation. 2000;102:2607–10.PubMedCrossRef
32.
Zurück zum Zitat Drager LF, Bortolotto LA, Maki-Nunes C, Trombetta IC, Alves MJNN, Fraga RF, et al. The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome. Atherosclerosis. 2010;208:490–5.PubMedCrossRef Drager LF, Bortolotto LA, Maki-Nunes C, Trombetta IC, Alves MJNN, Fraga RF, et al. The incremental role of obstructive sleep apnoea on markers of atherosclerosis in patients with metabolic syndrome. Atherosclerosis. 2010;208:490–5.PubMedCrossRef
33.
Zurück zum Zitat Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62(7):569–76.PubMedPubMedCentralCrossRef Drager LF, Togeiro SM, Polotsky VY, Lorenzi-Filho G. Obstructive sleep apnea: a cardiometabolic risk in obesity and the metabolic syndrome. J Am Coll Cardiol. 2013;62(7):569–76.PubMedPubMedCentralCrossRef
34.
Zurück zum Zitat Young T, Finn L, Peppard PE, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31:1071–8.PubMedPubMedCentral Young T, Finn L, Peppard PE, et al. Sleep disordered breathing and mortality: eighteen-year follow-up of the Wisconsin sleep cohort. Sleep. 2008;31:1071–8.PubMedPubMedCentral
35.
Zurück zum Zitat Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046–53.PubMedCrossRef Marin JM, Carrizo SJ, Vicente E, Agusti AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005;365:1046–53.PubMedCrossRef
36.
Zurück zum Zitat Light M, McCowen K, Malhotra A, Mesarwi OA. Sleep apnea, metabolic disease, and the cutting edge of therapy. Metabolism. 2018;84:94–8.PubMedCrossRef Light M, McCowen K, Malhotra A, Mesarwi OA. Sleep apnea, metabolic disease, and the cutting edge of therapy. Metabolism. 2018;84:94–8.PubMedCrossRef
37.
Zurück zum Zitat Dehvari N, da Silva Junior ED, Bengtsson T, Hutchinson DS. Mirabegron: potential off target effects and uses beyond the bladder. Br J Pharmacol. 2018;175(21):4072–82.PubMedPubMedCentralCrossRef Dehvari N, da Silva Junior ED, Bengtsson T, Hutchinson DS. Mirabegron: potential off target effects and uses beyond the bladder. Br J Pharmacol. 2018;175(21):4072–82.PubMedPubMedCentralCrossRef
38.
Zurück zum Zitat van Gelderen M, Stölzel M, Meijer J, Kerbusch V, Collins C, Korstanje C. An exploratory study in healthy male subjects of the mechanism of mirabegron-induced cardiovascular effects. J Clin Pharmacol. 2017;57(12):1534–44.PubMedCrossRef van Gelderen M, Stölzel M, Meijer J, Kerbusch V, Collins C, Korstanje C. An exploratory study in healthy male subjects of the mechanism of mirabegron-induced cardiovascular effects. J Clin Pharmacol. 2017;57(12):1534–44.PubMedCrossRef
39.
Zurück zum Zitat Hatanaka T, Ukai M, Watanabe M, Someya A, Ohtake A, Suzuki M, et al. In vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats. Naunyn Schmiedeberg's Arch Pharmacol. 2013;386(3):247–53.CrossRef Hatanaka T, Ukai M, Watanabe M, Someya A, Ohtake A, Suzuki M, et al. In vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats. Naunyn Schmiedeberg's Arch Pharmacol. 2013;386(3):247–53.CrossRef
40.
Zurück zum Zitat Black SM. β3-Adrenoceptor, glutathionylation, and diabetic cardiomyopathy. Focus on “beta3 adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade”. Am J Phys Cell Phys. 2015;309:C283–5. Black SM. β3-Adrenoceptor, glutathionylation, and diabetic cardiomyopathy. Focus on “beta3 adrenoceptor activation relieves oxidative inhibition of the cardiac Na+-K+ pump in hyperglycemia induced by insulin receptor blockade”. Am J Phys Cell Phys. 2015;309:C283–5.
41.
Zurück zum Zitat Leo S, Gattuso A, Mazza R, et al. Cardiac influence of the β3-adrenoceptor in the goldfish (Carassius auratus): a protective role under hypoxia? J Exp Biol. 2019;222(Pt 19):jeb211334. Published 2019 Oct 10.PubMedCrossRef Leo S, Gattuso A, Mazza R, et al. Cardiac influence of the β3-adrenoceptor in the goldfish (Carassius auratus): a protective role under hypoxia? J Exp Biol. 2019;222(Pt 19):jeb211334. Published 2019 Oct 10.PubMedCrossRef
42.
Zurück zum Zitat Sikarwar AS, Hinton M, Santhosh KT, Dhanaraj P, Talabis M, Chelikani P, et al. Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn. Am J Phys Lung Cell Mol Phys. 2018;315(6):L933–44. Sikarwar AS, Hinton M, Santhosh KT, Dhanaraj P, Talabis M, Chelikani P, et al. Hypoxia inhibits adenylyl cyclase catalytic activity in a porcine model of persistent pulmonary hypertension of the newborn. Am J Phys Lung Cell Mol Phys. 2018;315(6):L933–44.
43.
Zurück zum Zitat Wiktorowska-Owczarek A, Owczarek J. The effect of hypoxia on PGE2-stimulated cAMP generation in HMEC-1. Cell Mol Biol Lett. 2015;20(2):213–21.PubMedCrossRef Wiktorowska-Owczarek A, Owczarek J. The effect of hypoxia on PGE2-stimulated cAMP generation in HMEC-1. Cell Mol Biol Lett. 2015;20(2):213–21.PubMedCrossRef
44.
Zurück zum Zitat Lee LC, Maurice DH, Baillie GS. Targeting protein-protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease. Future Med Chem. 2013;5(4):451–64.PubMedCrossRef Lee LC, Maurice DH, Baillie GS. Targeting protein-protein interactions within the cyclic AMP signaling system as a therapeutic strategy for cardiovascular disease. Future Med Chem. 2013;5(4):451–64.PubMedCrossRef
45.
Zurück zum Zitat Milano S, Gerbino A, Schena G, Carmosino M, Svelto M, Procino G. Human β3-adrenoreceptor is resistant to agonist-induced desensitization in renal epithelial cells. Cell Physiol Biochem. 2018;48(2):847–62.PubMedCrossRef Milano S, Gerbino A, Schena G, Carmosino M, Svelto M, Procino G. Human β3-adrenoreceptor is resistant to agonist-induced desensitization in renal epithelial cells. Cell Physiol Biochem. 2018;48(2):847–62.PubMedCrossRef
46.
Zurück zum Zitat Ursino MG, Vasina V, Raschi E, et al. The beta3-adrenoceptor as a therapeutic target: current perspectives. Pharmacol Res. 59(4):221–34. Ursino MG, Vasina V, Raschi E, et al. The beta3-adrenoceptor as a therapeutic target: current perspectives. Pharmacol Res. 59(4):221–34.
Metadaten
Titel
Mirabegron Ameliorated Atherosclerosis of ApoE−/− Mice in Chronic Intermittent Hypoxia but Not in Normoxia
verfasst von
Yue Wang
Yue Wang
Hong-feng Jiang
Hai-ming Dang
Meng-ru Liu
Xin-yan Liu
Yang Yu
Jiang Xie
Xiao-jun Zhan
Hui-na Zhang
Xiao-fan Wu
Publikationsdatum
21.06.2021
Verlag
Springer US
Erschienen in
Cardiovascular Drugs and Therapy / Ausgabe 5/2022
Print ISSN: 0920-3206
Elektronische ISSN: 1573-7241
DOI
https://doi.org/10.1007/s10557-021-07196-w

Weitere Artikel der Ausgabe 5/2022

Cardiovascular Drugs and Therapy 5/2022 Zur Ausgabe

So beeinflussen Herzinfarkte auf lange Sicht die Sterblichkeit

20.06.2024 ST-Hebungsinfarkt Nachrichten

Wie hoch ist bei Patienten, die nach einem ST-Hebungs-Myokardinfarkt die initiale Hochrisikophase überleben, auf lange Sicht das Sterberisiko? Eine Studie aus Dänemark liefert dazu nun aufschlussreiche Daten.

Protonenpumpenhemmer stoppt Arrhythmie

20.06.2024 Protonenpumpenhemmstoffe Nachrichten

Wenn Nervenfasern aus dem Magen und dem Herzen im Gehirn dicht beieinander liegen, kann auch mal etwas schiefgehen: So lässt sich erklären, weshalb Schmerzen durch einen Magentumor bei einem Mann eine ventrikuläre Extrasystolie auslösen – und PPI diese beenden.

Ob Apixaban nützt oder schadet, entscheidet der CHA2DS2-VASc-Score

20.06.2024 Therapie des Vorhofflimmerns Nachrichten

Patienten mit subklinischem Vorhofflimmern tragen ein erhöhtes Risiko für Schlaganfälle. Da stellt sich die Frage nach einer medikamentösen Antikoagulation. Offenbar hängt es aber vom CHA2DS2-VASc-Score ab, ob die Gabe von Apixaban von Vorteil ist.

Wie SGLT2-Hemmer es schaffen, die Mortalität zu reduzieren

20.06.2024 Kardiologische Therapie Nachrichten

SGLT2-Hemmer verhindern keine Herzinfarkte oder Schlaganfälle. Aber sie reduzieren die kardiovaskuläre Mortalität bei einem breiten Spektrum von Patienten. Wie sie das schaffen, verdeutlicht eine Metaanalyse von Daten aus elf randomisierten Studien.

Update Kardiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.