ArticleJournal of the American Heart Association2021
Paroxetine Attenuates Cardiac Hypertrophy Via Blocking GRK2 and ADRB1 Interaction in Hypertension.
Article in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Inhibition of the serotonin transporter and risk of heart valve disease: A systematic review and meta-analysis.European journal of pharmacology · 2026Pooled it
- Recent advances in the development of GRK2 inhibitors: blocking the interaction of GRK2 with its partners.Acta pharmacologica Sinica · 2026Review
- Psychological Scars and Physical Consequences: Linking PTSD to Cardiovascular Health.Journal of cardiovascular translational research · 2026Review
- Regulation of G protein-coupled receptor kinase 2 and its role in tumors.Journal of translational medicine · 2026Review
- Drug Repositioning in Doxorubicin-Induced Cardiotoxicity Protection.International journal of molecular sciences · 2025Review
- Evolving Cardioprotective Strategies in Cardio-Oncology: A Narrative Review.Current cardiology reports · 2025Review
- Exploiting host kinases to combat dengue virus infection and disease.Antiviral research · 2025Review
- A Novel Study of β1- and β2-Adrenergic Receptors Present on PBMCs, T Cells, Monocytes, and NK Cells by Radioligand Method: Quantitation and Correlations.International journal of molecular sciences · 2025Article
- Logic-based machine learning predicts how escitalopram attenuates cardiomyocyte hypertrophy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Therapeutic Efficacy of a Novel Pharmacologic GRK2 Inhibitor in Multiple Animal Models of Heart Failure.JACC. Basic to translational science · 2025Article
- Global Research Trends and Focus on the Link Between Heart Failure and NLRP3 Inflammasome: A Bibliometric Analysis From 2010 to 2024.Journal of multidisciplinary healthcare · 2025Review
- Active ingredients of traditional Chinese medicine inhibit NOD-like receptor protein 3 inflammasome: a novel strategy for preventing and treating heart failure.Frontiers in immunology · 2025Review
- Potential cardioprotective effect of paroxetine against ventricular remodeling in an animal model of myocardial infarction: a comparative study.BMC pharmacology & toxicology · 2024Article
- Deciphering the genetic interplay between depression and dysmenorrhea: a Mendelian randomization study.Briefings in bioinformatics · 2024Article
- G protein-coupled receptor kinases in hypertension: physiology, pathogenesis, and therapeutic targets.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Review
- The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension.Journal of molecular and cellular cardiology plus · 2024Article
- Hypertensive Heart Disease: Mechanisms, Diagnosis and Treatment.Reviews in cardiovascular medicine · 2024Review
- Augmentation of Endothelial S1PR1 Attenuates Postviral Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- Regional variation in accessibility of automated external defibrillators in British Columbia.CJEM · 2024Article
- Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background ADRB1 (adrenergic receptor beta 1) responds to neuroendocrine stimulations, which have great implications in hypertension. GRK2 (G protein-coupled receptor kinase 2) is an essential regulator for many G protein-coupled receptors and subsequent cell signaling cascades, but its role as a regulator of ADRB1 and associated cardiac hypertrophy in hypertension remains to be elucidated. Methods and Results In this study, we found the expressions of GRK2 and ADRB1 in peripheral blood mononuclear cells were positively associated with blood pressure levels in hypertensive patients and with their expression in heart. In vitro evidence showed a direct interaction in ADRB1 and GRK2 and genetic depletion of GRK2 blocks epinephrine-induced upregulation of hypertrophic and fibrotic genes in cardiomyocytes. Meanwhile, we discovered a selective serotonin reuptake inhibitor paroxetine specifically blockades GRK2 and ADRB1 interaction. In vivo, paroxetine treatment ameliorates hypertension-induced cardiac hypertrophy, dysfunction, and fibrosis in animal models. We found that paroxetine suppressed sympathetic overdrive and increased the adrenergic receptor sensitivity to catecholamines. Paroxetine treatment also blocks epinephrine-induced upregulation of hypertrophic and fibrotic genes as well as ADRB1 internalization in cardiomyocytes. Coadministration of paroxetine further potentiates metoprolol-induced reductions in blood pressure and heart rate, further attenuating cardiac hypertrophy in spontaneously hypertensive rats. Furthermore, in patients with hypertension accompanied with depression, we observed that cardiac remodeling was less severe in those with paroxetine treatment compared with those with other types of anti-depressive agents. Conclusions Paroxetine promotes ADRB1 sensitivity and attenuates cardiac hypertrophy partially via blocking GRK2-mediated ADRB1 activation and internalization in the context of hypertension.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.