|
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 |
GeneticVariation
|
disease |
BEFREE |
Thus, sensitization of the heart failure-promoting AT1 receptor by the RKIP-GRK2 interaction contributes to heart failure whereas dominant-negative GRK2-K220R is cardioprotective.
|
30687708 |
2018 |
|
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 |
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 |
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 |
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 |
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 |
|
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 |
|
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 |
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 |
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 |
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 |
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 |