|
Heart failure
|
0.600 |
Therapeutic
|
disease |
RGD |
(-)-Epigallocatechin-3-gallate, the major green tea catechin, regulates the desensitization of β1 adrenoceptor via GRK2 in experimental heart failure.
|
29247373 |
2018 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
(-)-Epigallocatechin-3-gallate, the major green tea catechin, regulates the desensitization of β1 adrenoceptor via GRK2 in experimental heart failure.
|
29247373 |
2018 |
|
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 |
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 |
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 |
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 |
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 |
|
Heart failure
|
0.600 |
AlteredExpression
|
disease |
BEFREE |
Besides the reported upregulation of beta-adrenergic receptor kinase-1 in heart failure, we observed new gene expression patterns, such as the upregulation of fas-activated serine/threonine kinase (FAST) or reduced expression of desmoplakin.
|
18649053 |
2008 |
|
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 |
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 |
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 |
Furthermore, inhibition of G(i) signaling with pertussis toxin restores cardiac function in heart failure associated with increased β(2)AR to G(i) coupling induced by removing PKA phosphorylation of the receptor and in GRK2 transgenic mice, indicating that enhanced phosphorylation of β(2)AR by GRK and resultant increase in G(i)-biased β(2)AR signaling play an important role in the development of heart failure.
|
22179058 |
2012 |
|
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 |
Herein, we will update the readers about the 'state-of-art' of GRK2 inhibition as a potent therapeutic strategy in HF.
|
29166798 |
2018 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Higher βARK1 is associated with worse physical HF symptoms, pinpointing a potential pathophysiologic underpinning.
|
29803296 |
2019 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
However, the mechanisms of how GRK2 directly contributes to the pathogenesis of HF need further investigation, and additional verification of the mechanistic details are needed before GRK2 inhibition can be used for the treatment of HF.
|
24702056 |
2014 |
|
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 |
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 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
In addition, chronic overexpression of GRK2 inhibits catecholamine induction of vital positive chronotropic and ionotropic effects required to preserve cardiac output leading to worsening of congestive HF.
|
27222484 |
2017 |
|
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 |
AlteredExpression
|
disease |
BEFREE |
In the heart, the major GRK isoforms, GRK2 and GRK5, undergo upregulation due to the heightened sympathetic nervous system activity that is characteristic of HF as catecholamine levels increase in an effort to drive the failing pump.
|
21622221 |
2011 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Increased GRK2 correlates with clinical severity using the INTERMACS scale and LV stroke volume, supporting it as a potential target in advanced HF.
|
22196842 |
2012 |
|
Heart failure
|
0.600 |
Biomarker
|
disease |
BEFREE |
Increased Atrial β-Adrenergic Receptors and GRK-2 Gene Expression Can Play a Fundamental Role in Heart Failure After Repair of Congenital Heart Disease with Cardiopulmonary Bypass.
|
28214967 |
2017 |
|
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 |