β-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion

Oliver, Eduardo; Rovira, Eduardo; Montó, Fermí; Valldecabres, Carmen; Julve, R; Muedra, Vicente; Ruiz, Nuria; Barettino, Domingo; D’Ocón, Pilar

doi:10.1097/hjh.0b013e3283383564

Cited by 25 publications

(32 citation statements)

References 35 publications

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“…Abundance of the three different GRKs characterized in the heart follows the order GRK5 Ͼ GRK2 Ն GRK3 and corroborates previous data in the human heart (20,33,35). A nonsignificant increase in the expression of the three GRKs was observed in FH, but an interesting result not previously evidenced is the higher expression of GRK3 and GRK5 associated with a lower degree of the LVESD or LVEDD, adding new information to previous findings supporting a protective role for GRK3 in the cardiovascular system (28,38) and contributing to a better understanding of the position of the GRK3 gene in a locus on a chromosome associated with LV mass and contractility (4). The inverse correlation found between the GRK5 expression (a kinase that modulates cardiac ␤ 1 activity) and cardiac hypertrophy supports clinical evidence for a protective role of a GRK5 polymorphism in HF that inhibits ␤ 1 -AR signaling more effectively (20).…”

Section: What Happens With Cardiac ␣ 1 -Ars In Hf?supporting

confidence: 89%

“…The frozen samples were ground to powder in a mortar and divided into three portions. One portion was used to obtain total RNA as previously described (1,2,28), and the other two portions were reserved to obtain total proteins or binding assays. Total RNA was quantified and analyzed by running 1 g of each sample by microfluidic electrophoresis using the Experion automated electrophoresis system (Bio-Rad, Madrid, Spain) following the manufacture's conditions.…”

Section: Methodsmentioning

confidence: 99%

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Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables

Montó

Oliver

Vicente

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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. Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables. Am J Physiol Heart Circ Physiol 303: H368 -H376, 2012. First published June 8, 2012; doi:10.1152/ajpheart.01061.2011.-Downregulation of ␤ 1-adrenergic receptors (␤ 1-ARs) and increased expression/function of G-protein-coupled receptor kinase 2 (GRK2) have been observed in human heart failure, but changes in expression of other ARs and GRKs have not been established. Another unresolved question is the incidence of these compensatory mechanisms depending on heart failure etiology and treatment. To analyze these questions, we quantified the mRNA/protein expressions of six ARs (␣ 1A, ␣1B, ␣1D, ␤1, ␤ 2, and ␤3) and three GRKs (GRK2, GRK3, and GRK5) in left (LV) and right ventricle (RV) from four donors, 10 patients with ischemic cardiomyopathy (IC), 14 patients with dilated cardiomyopathy (DC), and 10 patients with nonischemic, nondilated cardiopathies (NINDC). We correlated the changes in the expressions of ARs and GRKs with clinical variables such as left ventricular ejection fraction (LVEF) and left ventricular end-systolic and left ventricular end-diastolic diameter (LVESD and LVEDD, respectively). The main findings were 1) the expression of the ␣ 1A-AR in the LV positively correlates with LVEF; 2) the expression of GRK3 and GRK5 inversely correlates with LVESD and LVEDD, supporting previous observations about a protective role for both kinases in failing hearts; and 3) ␤ 1-AR expression is downregulated in the LV and RV of IC, in the LV of DC, and in the RV of NINDC. This difference, better than an increased expression of GRK2 (not observed in IC), determines the lower LVEF in IC and DC vs. NINDC. G-protein-coupled receptor kinasesHUMAN HEART FAILURE (HF) is recognized as a major public health problem arising from multiple causes that will affect one in five adults, conferring elevated mortality rates (20). Regardless of the cause, multiple organ systems attempt to compensate for the deteriorating heart and the sympathetic nervous system responds to HF with increased activity, resulting in increased levels of catecholamines and in an enhanced stimulation of adrenergic receptors (ARs; 33). Consequently, catecholamines powerfully stimulate the heart function at the expense of overproportional increases in energy consumption (13). This is a nonrigid signaling system that adapts to continuous stimulation by reducing the abundance of ␤ 1 -ARs and increasing the expression and enzymatic activity of G-proteincoupled receptor kinases (GRKs), which phosphorylate agonist-occupied receptors and facilitate their endocytosis and desensitization (26). As a result of these adaptations, cardiomyocytes in failing hearts (FH) lose their responsiveness to catecholamines over time (13).In spite of this simple scenario, many fundamental questions remain unanswered. The heart expresses different ␤-ARs (␤ 1 , ␤ 2 , and ␤ 3 ) and ␣ 1 -ARs (␣ 1A , ␣ 1B , and ␣ 1D

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Section: What Happens With Cardiac ␣ 1 -Ars In Hf?supporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables

Montó

Oliver

Vicente

et al. 2012

American Journal of Physiology-Heart and Circulatory Physiology

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“…A decreased β-AR function has been reported in heart failure, which may also be associated with SAN dysfunction (28). In this case, SAN failure occurs via a decreased β-AR expression, together with an increase in GRK activity in the heart and mirrored in some cases, in peripheral blood mononuclear cells (28)(29)(30)(31), both in humans (28,29,(32)(33)(34)(35) and in experimental models (34)(35)(36)(37)(38). A decreased expression and an increased desensitization of β-AR directly led to a loss of β-adrenergic function in the failing heart (28).…”

Section: R420qmentioning

confidence: 90%

RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism

Wang¹,

Mesirca²,

Marqués-Sulé³

et al. 2017

JCI Insight

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“…The ␤ 1 -AR gene expression was higher in regulatory T cells compared to other T-cell populations [17] . The overexpression of ␤ 1 -AR has been detected in peripheral lymphocytes from hypertensive patients and patients with congestive heart disease after drug treatment [18,19] . The ␤ 1 -AR mRNA level in lymphocytes directly correlated with urinary albumin excretion in microalbuminuric patients [19] .…”

mentioning

confidence: 99%

“…Administration of the ␤ 3 -AR agonist increased the number but not the proliferation of cluster of differentiation 4 positive (CD4+) and CD8+ T lymphocytes in the spleen of obese animals [20] . The ␤ 3 -AR mRNA was detected in human peripheral lymphocytes [18,19,21] , but functional significance has not yet been investigated.…”

mentioning

confidence: 99%

Acute Stress Differently Modulates Beta 1, Beta 2 and Beta 3 Adrenoceptors in T Cells, but Not in B Cells, from the Rat Spleen

Lauková

Vargovič²,

Csáderová³

et al. 2012

Neuroimmunomodulation

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Objectives: Stress-induced rise in circulating catecholamines (CAs), followed by modulation of β-adrenergic receptors (adrenoceptors, ARs), is one of the pathways involved in the stress-mediated effects of immune functions. The spleen is an organ with a high number of lymphocytes and provides a unique microenvironment in which they reside. Thus, lymphocytes may respond differently to CAs in the spleen than in the circulation. No reports exist concerning the involvement of β-ARs in stress-mediated effects on T and B cells isolated from the spleen. Therefore, our aim was to investigate the effect of single stress exposure on gene expression and cellular localization of β-adrenoceptor subtypes in splenic T and B cells. We tried to correlate changes in adrenoceptors with the expression of apoptotic proteins. Methods: Immobilization (IMMO) was used as a stress model. T and B cells were isolated from rat spleen using magnetically labeled antibodies. The gene expression of individual adrenoceptors and apoptotic proteins was evaluated by real-time PCR. Immunofluorescence was used to evaluate localization and adrenoceptor expression. Results: We have found T cells to be more vulnerable to stress compared to B cells, because of increased β₁-, β₂- and β₃-ARs after a single IMMO. Moreover, β₂-ARs translocated from the nucleus to the plasma membrane in T cells after IMMO. The rise in β-ARs most probably led to the rise of Bax mRNA and Bax to Bcl-2 mRNA ratio. This might suggest the induction of an apoptotic process in T cells. Conclusion: Higher susceptibility of T cells to stress via modulation of β-ARs and apoptotic proteins might shift the immune responsiveness in the spleen.

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β-Adrenoceptor and GRK3 expression in human lymphocytes is related to blood pressure and urinary albumin excretion

Cited by 25 publications

References 35 publications

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables

Different expression of adrenoceptors and GRKs in the human myocardium depends on heart failure ethiology and correlates to clinical variables

RyR2R420Q catecholaminergic polymorphic ventricular tachycardia mutation induces bradycardia by disturbing the coupled clock pacemaker mechanism

Acute Stress Differently Modulates Beta 1, Beta 2 and Beta 3 Adrenoceptors in T Cells, but Not in B Cells, from the Rat Spleen

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