|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Last, we will update the readers on the current status of GRK2 inhibitors as a potential therapeutic strategy for heart failure with an emphasis on their ability of rescuing NO bioavailability.
|
28077324 |
2018 |
|
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 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Therefore, data support the use of the βARKct as a promising candidate for therapeutic application in human HF.
|
20800067 |
2011 |
|
Heart failure
|
0.600 |
GeneticVariation
|
disease |
BEFREE |
Reduction of sympathetic activity via adrenal-targeted GRK2 gene deletion attenuates heart failure progression and improves cardiac function after myocardial infarction.
|
20351116 |
2010 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure.
|
28699740 |
2017 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Over the last 20years, the role of GRK2 in HF has been widely studied.
|
26829117 |
2016 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
In animal models, GRK2 contributes to the pathogenesis of heart failure after ischemia-reperfusion (IR) injury.
|
30538174 |
2018 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Importantly, inhibition of GRK2 activity prevents postischemic defects in myocardial insulin signaling and improves cardiac metabolism via normalized glucose uptake, which appears to participate in GRK2-targeted prevention of heart failure.
|
21518983 |
2011 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
A vast body of literature has established GRK2 as a key player in the development and progression of heart failure.
|
30946029 |
2019 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
RGD |
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 |
|
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 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
CTD_human |
Conversely, the dual-specific GRK2 and ERK cascade inhibitor, RKIP (Raf kinase inhibitor protein), triggered dysfunctional cardiomyocyte energetics and the expression of heart failure-promoting Pparg-regulated genes.
|
26670611 |
2016 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
More consistent to mammalians, adult zebrafish developed significant heart failure in concert with β1-AR downregulation, and GRK2 and brain natriuretic peptide (BNP) upregulation in response to prolonged, 14d ISO-stimulation.
|
28554511 |
2017 |
|
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 |
|
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 |