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| 1 | Angiotensin receptor blocker drugs and inhibition of adrenal beta-arrestin-1-dependent aldosterone production: Implications for heart failure therapy显示文摘Aldosterone mediates many of the physiological and pathophysiological/cardio-toxic effects of angiotensin II(Ang II). Its synthesis and secretion from the zona glomerulosa cells of the adrenal cortex, elevated in chronic heart failure(HF), is induced by Ang II type 1 receptors(AT1Rs). The AT1R is a G protein-coupled receptor, mainly coupling to Gq/11 proteins. However, it can also signal through β-arrestin-1(βarr1) or-2(βarr2), both of which mediate G protein-independent signaling. Over the past decade, a second, Gq/11 proteinindependent but βarr1-dependent signaling pathway emanating from the adrenocortical AT1R and leading to aldosterone production has become appreciated. Thus, it became apparent that AT1R antagonists that block both pathways equally well are warranted for fully effective aldosterone suppression in HF. This spurred the comparison of all of the currently marketed angiotensin receptor blockers(ARBs, AT1R antagonists or sartans) at blocking activation of the two signaling modes(G protein-, and βarr1-dependent) at the Ang IIactivated AT1R and hence, at suppression of aldosterone in vitro and in vivo. Although all agents are very potent inhibitors of G protein activation at the AT1R, candesartan and valsartan were uncovered to be the most potent ARBs at blocking βarr activation by Ang II and at suppressing aldosterone in vitro and in vivo in post-myocardial infarction HF animals. In contrast, irbesartan and losartan are virtually G protein-'biased' blockers at the human AT1R, with very low efficacy for βarr inhibition and aldosterone suppression. Therefore, candesartan and valsartan(and other, structurally similar compounds) may be the most preferred ARB agents for HF pharmacotherapy, as well as for treatment of other conditions characterized by elevated aldosterone. | Anastasios Lymperopoulos Beatrix Aukszi | 2017 | World Journal of Cardiology2017，9，3： | 11 |
| 2 | Adrenal G protein-coupled receptor kinase-2 in regulation of sympathetic nervous system activity in heart failure显示文摘Heart failure(HF), the number one cause of death in the western world, is caused by the insufficient performance of the heart leading to tissue underperfusion in response to an injury or insult. It comprises complex interactions between important neurohormonal mechanisms that try but ultimately fail to sustain cardiac output. The most prominent such mechanism is the sympathetic(adrenergic) nervous system(SNS), whose activity and outflow are greatly elevated in HF. SNS hyperactivity confers significant toxicity to the failing heart and markedly increases HF morbidity and mortality via excessive activation of adrenergic receptors, which are G protein-coupled receptors. Thus, ligand binding induces their coupling to heterotrimeric G proteins that transduce intracellular signals. G protein signaling is turned-off by the agonist-bound receptor phosphorylation courtesy of G protein-coupled receptor kinases(GRKs), followed by βarrestin binding, which prevents the GRK-phosphorylated receptor from further interaction with the G proteins and simultaneously leads it inside the cell(receptor sequestration). Recent evidence indicates that adrenal GRK2 and βarrestins can regulate adrenal catecholamine secretion, thereby modulating SNS activity in HF. The present review gives an account of all these studies on adrenal GRKs and βarrestins in HF and discusses the exciting new therapeutic possibilities for chronic HF offered by targeting these proteins pharmacologically. | Katie A Mc Crink Ava Brill Anastasios Lymperopoulos | 2015 | World Journal of Cardiology2015，7，9： | 4 |
| 3 | Myocardial adeno - associated virus serotype 6 - betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure 显示文摘 | Rengo G Lymperopoulos A Zincarelli C | 2009 | Circulation2009，119，1： | 1 |
| 4 | Myocardial adeno - as-sociated virus serotype 6 - pARKct gene therapy improves cardiac func-tion and normalizes the neurohormonal axis in chronic heart failure显示文摘 | Rengo G Lymperopoulos A Zincarelli C | 2009 | Circulation2009，119，1： | 1 |
| 5 | Adrenergic nervous sys-tem in heart failure:pathophysiology and therapy 显示文摘 | Lymperopoulos A Rengo G Koch W J | 2013 | Circ Res2013，113，6： | 1 |
| 6 | Myocardial adeno-associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure显示文摘 | Rengo G Lymperopoulos A Zincarelli C | | 0，，： | 1 |
| 7 | GRK2 as a novel genetherapy target in heart failure显示文摘 | Rengo G Lymperopoulos A Leosco D | 2011 | J Mol Cell Cardiol2011，50，5： | 1 |
| 8 | GRK2 inhibition in heart failure:something old,something new显示文摘 | Lymperopoulos A Rengo G Koch WJ | | 0，，： | 1 |
| 9 | GRK2 inhibition in heartfailure: something old, something new显示文摘 | Lymperopoulos A Rengo G Koch WJ | 2012 | Curr Pharm Des2012，18，2： | 1 |
| 10 | Not all arrestins are created equal: Therapeutic implications of the functional diversity of the β-arrestins in the heart显示文摘The two ubiquitous, outside the retina, G protein-coupled receptor(GPCR)adapter proteins, β-arrestin-1 and-2(also known as arrestin-2 and-3,respectively), have three major functions in cells: GPCR desensitization, i.e.,receptor decoupling from G-proteins; GPCR internalization via clathrin-coated pits; and signal transduction independently of or in parallel to G-proteins. Bothβ-arrestins are expressed in the heart and regulate a large number of cardiac GPCRs. The latter constitute the single most commonly targeted receptor class by Food and Drug Administration-approved cardiovascular drugs, with about onethird of all currently used in the clinic medications affecting GPCR function.Since β-arrestin-1 and-2 play important roles in signaling and function of several GPCRs, in particular of adrenergic receptors and angiotensin II type 1 receptors,in cardiac myocytes, they have been a major focus of cardiac biology research in recent years. Perhaps the most significant realization coming out of their studies is that these two GPCR adapter proteins, initially thought of as functionally interchangeable, actually exert diametrically opposite effects in the mammalian myocardium. Specifically, the most abundant of the two β-arrestin-1 exerts overall detrimental effects on the heart, such as negative inotropy and promotion of adverse remodeling post-myocardial infarction(MI). In contrast, β-arrestin-2 is overall beneficial for the myocardium, as it has anti-apoptotic and antiinflammatory effects that result in attenuation of post-MI adverse remodeling,while promoting cardiac contractile function. Thus, design of novel cardiac GPCRligands that preferentially activate β-arrestin-2 over β-arrestin-1 has the potential of generating novel cardiovascular therapeutics for heart failure and other heart diseases. | Anastasios Lymperopoulos Shelby L Wertz Celina M Pollard Victoria L Desimine Jennifer Maning Katie A McCrink | 2019 | World Journal of Cardiology2019，11，2： | 1 |
| 11 | GRK2 as a novel gene therapy target in heart failure 显示文摘 | Rengo G Lymperopoulos A Leosco D | 2011 | J Mol Cell Cardio12011，50，5： | 1 |
| 12 | GRK2 as a novel gene therapy target in heart failure显示文摘 | Rengo G Lymperopoulos A Leosco D | | 0，，： | 1 |
| 13 | Adrenal adrenoceptors inheart failure: fine-tuning cardiac stimulation显示文摘 | Lymperopoulos A Rengo G Koch WJ | 2007 | Trends Mol Med2007，13，12： | 1 |
| 14 | Myocardial adeno-associated virus serotype 6-βARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure显示文摘 | Rengo G Lymperopoulos A Zincarelli C | | 0，，： | 1 |
| 15 | Reduction of sympatheticactivity via adrenal-targeted GRK2 gene deletion attenuates heartfailure progression and improves cardiac function after myocardialinfarction显示文摘 | Lymperopoulos A Rengo G Gao E | 2010 | J Biol Chem2010，285，16： | 1 |
| 16 | Myocardial adeno- associated virus serotype 6-betaARKct gene therapy improves cardiac function and normalizes the neurohormonal axis in chronic heart failure显示文摘 | Rengo G Lymperopoulos A Zincarelli C | 2009 | Circulation2009，119，1： | 1 |
| 17 | Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction显示文摘 | Lymperopoulos A Rengo G Gao E | 2010 | J Biol Chem2010，285，16： | 1 |
| 18 | The effect of per-sonality traits on private brand consumertendencies:A cross-cultural study of Medi-terranean countries显示文摘 | RamHerstein’Sigal TifFeretJose LuisAbrantes Constantine Lymperopoulos TahirAlbayrak Meltem Caber | 2012 | Cross CulturalManagement:An International Journal2012，，： | 1 |
| 19 | β-Adrenergic receptor blockade restores the GRK2-mediated adrenal α2-adrenergic receptor-catecholamine production axis in heart failure显示文摘 | Rengo G Lymperopoulos A Zincarelli C | 2012 | Br J Pharmacol2012，166，8： | 1 |
| 20 | Adrenergic nervous system in heart failure : pa-thophysiology and therapy 显示文摘 | Lymperopoulos A Rengo G Koch WJ | 2013 | Circ Res2013，113，6： | 1 |
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