|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
GRK2 levels and activity have been reported to be enhanced in patients or in preclinical models of several relevant pathological situations, such as heart failure, cardiac hypertrophy, hypertension, obesity and insulin resistance conditions, or non-alcoholic fatty liver disease (NAFLD), and to contribute to disease progression by a variety of mechanisms related to its multifunctional roles.
|
30837878 |
2019 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
It has been shown that lowering cardiac G-protein-coupled-receptor-kinase-2 (GRK2) activity with βARKct expression, a peptide inhibitor of protein-coupled-receptor-kinase-2 (GRK2), results in improvement of heart failure in several different animal models.
|
30782477 |
2019 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Higher βARK1 is associated with worse physical HF symptoms, pinpointing a potential pathophysiologic underpinning.
|
29803296 |
2019 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
The increase in protein activity and upregulation of G-protein coupled receptor kinase 2 (GRK2) is a hallmark of cardiac stress and heart failure.
|
28759639 |
2017 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
One of these newly discovered cardiotoxic effects of GRK2, uncovered by our laboratory, is promotion by adrenal GRK2 of sympathetic hyperactivity of the failing heart, a significant morbidity factor in HF, targeted therapeutically nowadays by the use of beta-blockers in HF pharmacotherapy.
|
22229578 |
2012 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The gene expression pattern of GRK2 and β2-adrenoceptor as molecular markers of cardiac dysfunction was altered in patients with severe PR compared with controls and was similar to expression in patients with advanced HF.
|
30104167 |
2019 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling.
|
31785110 |
2020 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
LVAD treatment in children with heart failure results in reversal of several pathologic myocellular processes, and G protein-coupled receptor kinase-2 may regulate β<sub>1</sub>-AR but not β<sub>2</sub>-adrenergic receptor expression in children with heart failure.
|
27908653 |
2017 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Importantly, cardiac dysfunction was preceded by elevated betaARK1 levels and activity, thus suggesting that betaARK1 may be a precipitating factor in the transition from hypertension-induced compensatory cardiac hypertrophy to HF.
|
9931137 |
1999 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Small molecule Gβγ-GRK2 inhibition initiated 1 week post-injury was cardioprotective in the I/R model of chronic HF, including preservation of cardiac contractility and a reduction in cardiac fibrotic remodeling.
|
28818206 |
2017 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Given that increased expression and activity of GRK2 and GRK5 contribute to the loss of contractile reserve in the stressed and failing heart, inhibition of overactive GRKs has been proposed as a novel therapeutic approach to treat heart failure.
|
31186538 |
2019 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Over the last 20years, the role of GRK2 in HF has been widely studied.
|
26829117 |
2016 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Its absolute values were approximately 350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. beta-Arrestin-2 levels were too low to be detectable using the same methods. beta ARK levels as determined by enzymatic activity were approximately 20 fmol/mg cytosolic protein (beta ARK-1 plus beta ARK-2) and thus almost 20-fold lower than those of beta-arrestin. beta ARK levels were increased approximately twofold in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
|
8293560 |
1994 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We also show human data consistent with MR activation status in heart failure influencing GRK2 levels.
|
26932512 |
2016 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
This review summarizes what is currently known regarding the activity of these kinases, and particularly the role of GRK2 and GRK5 in the molecular alterations that occur during heart failure.
|
28328744 |
2017 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Alternation of GRK2 protein level and activity casts profound effects on cell physiological functions and causes diseases such as heart failure, rheumatoid arthritis, and obesity.
|
23460259 |
2013 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Since GRK2 has been shown to compromise fatty acid (FA) oxidation, this kinase may link metabolic and contractile defects in HF.
|
30171848 |
2018 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
The expression of G protein-coupled receptor kinase 2 (GRK2), a key signaling hub, is up-regulated in the long-term in patients and in experimental models of heart failure.
|
31594751 |
2019 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
G protein-coupled receptor kinase 2 (GRK2) is a serine/threonine kinase that is involved in a variety of important signaling pathways and alternation of GRK2 protein level or activity causes diseases such as heart failure, rheumatoid arthritis, and obesity.
|
26936374 |
2016 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Among them, GRK2 has been described to be upregulated in many pathological conditions and its crucial role in cardiac hypertrophy, hypertension, and heart failure promoted the search for pharmacological inhibitors of its activity.
|
31525427 |
2019 |
|
Congestive heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
We will then focus on recent in vivo gene therapy strategies using the targeted inhibition of the betaAR kinase (betaARK1 or GRK2) and the restoration of S100A1 protein expression to support the injured heart and to reverse or prevent HF.
|
17602988 |
2007 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Recent advances in transgenic and gene therapy techniques have presented novel therapeutic strategies for management of heart failure via genetic manipulation of beta-AR signaling including the targeted inhibition of the beta-AR kinase (betaARK1 or GRK2).
|
15524162 |
2004 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Over the past two decades the GRK2 inhibitory peptide betaARKct has been identified as a potential therapy that is able to break this vicious cycle of self-perpetuating deregulation of the beta-AR system and subsequent myocardial malfunction, thus halting development of cardiac failure.
|
20623214 |
2010 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
This study may be used in designing more potent and selective GRK2 inhibitors for therapeutic intervention of heart failure.
|
31506468 |
2019 |
|
Congestive heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Downregulation of β(1)- adrenergic receptors (β(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.
|
22685168 |
2012 |