G-Protein–Coupled Receptors in Heart Disease

Wang, Jialu; Gareri, Clarice; Rockman, Howard A.

doi:10.1161/circresaha.118.311403

Cited by 204 publications

(181 citation statements)

References 272 publications

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“…Chronic stimulation of these receptors, including stimulation of badrenergic receptors (bARs) by catecholamines, drives cardiac hypertrophy and ventricular remodeling, ultimately leading to heart failure. The efficacy of b-blocker therapy for treatment of heart failure results, at least in part, by ameliorating chronic bAR stimulation in the heart (4,5).…”

Section: Introductionmentioning

confidence: 99%

Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy

Nash

Wei

Irannejad³

et al. 2019

Preprint

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Increased adrenergic tone resulting from cardiovascular stress leads to development of heart failure, in part, through chronic stimulation of b1 adrenergic receptors (bARs) on cardiac myocytes. Blocking these receptors is part of the basis for b-blocker therapy for heart failure. Recent data demonstrate that G protein-coupled receptors (GPCRs), including bARs, are activated intracellularly, although the biological significance is unclear. Here we investigated the functional role of Golgi bARs in cardiac myocytes and found they activate Golgi localized, prohypertrophic, phosphoinositide hydrolysis, that is not accessed by cell surface bAR stimulation. This pathway is accessed by the physiological neurotransmitter norepinephrine (NE) via an Oct3 organic cation transporter. Blockade of Oct3 or specific blockade of Golgi resident b1ARs prevents NE dependent cardiac myocyte hypertrophy. This clearly defines a physiological pathway activated by internal GPCRs in a biologically relevant cell type and has implications for development of more efficacious b-blocker therapies.

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Section: Introductionmentioning

confidence: 99%

Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy

Nash

Wei

Irannejad³

et al. 2019

Preprint

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“…Bk is a peptide that acts through a G-protein coupled receptor (GPCR) and is one of the most important mediators of PC [23]. It is well known that receptors belonging to the GPCR family trigger PC [24]. In this regard, it has been demonstrated that adenosine and opioid receptors mediate PC-induced cytoprotection in the heart.…”

Section: Discussionmentioning

confidence: 99%

Autocrine Bradykinin Release Promotes Ischemic Preconditioning-Induced Cytoprotection in Bovine Aortic Endothelial Cells

Bellis

Sorriento²,

Fiordelisi³

et al. 2020

IJMS

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The aims of this study were to assess whether ischemic preconditioning (PC) induces bradykinin (Bk) synthesis in bovine aortic endothelial cells (bAECs) and, if so, to explore the molecular mechanisms by which this peptide provides cytoprotection against hypoxia. PC was induced by exposing bAECs to three cycles of 15 min of hypoxia followed by 15 min of reoxygenation. Bk synthesis peaked in correspondence to the early and late phases of PC (10−12 M and 10−11 M, respectively) and was abolished by a selective tissue kallikrein inhibitor, aprotinin. Stimulation with exogenous Bk at concentrations of 10−12 M and 10−11 M reduced the cell death induced by 12 h of hypoxia by 50%. Pretreatment with HOE−140, a Bk receptor 2 (BKR2) inhibitor, in bAECs exposed to 12 h of hypoxia, abrogated the cytoprotective effect of early and late PC, whereas des-Arg-HOE-140, a Bk receptor 1 (BKR1) inhibitor, affected only the late PC. In addition, we found that PC evoked endocytosis and the recycling of BKR2 during both the early and late phases, and that inhibition of these pathways affected PC-mediated cytoprotection. Finally, we evaluated the activation of PKA and Akt in the presence or absence of BKR2 inhibitor. HOE-140 abrogated PKA and Akt activation during both early and late PC. Consistently, BKR2 inhibition abolished cross-talk between PKA and Akt in PC. In bAECs, Bk-synthesis evoked by PC mediates the protection against both apoptotic and necrotic hypoxia-induced cell death in an autocrine manner, by both BKR2- and BKR1-dependent mechanisms.

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“…GBP subunit alpha-11, called as "G protein", plays a central physiological role in the regulation of cardiac contractility by neurohumoral signals (37,38). In addition, G proteins modulate the binding of angiotensin-II to adrenal cortex receptors in the homeostatic regulation of the cardiovascular system (39,40).…”

Section: Discussionmentioning

confidence: 99%

Platelet Proteome Changes in Dogs with Chronic Heart Failure

Levent

Kocatürk

Akgun

et al. 2020

Preprint

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Background: Platelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in chronic heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n=10) and dogs with CHF due to myxomatous mitral valve degeneration (n=10) were used. Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris. Results: Totally 107 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in the CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in the CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses.Conclusion: This study describes by first time the changes in the protein composition in platelets of dogs with CHF. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF and could be a tool for further investigations about the prevention and treatment of this disease.

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G-Protein–Coupled Receptors in Heart Disease

Cited by 204 publications

References 272 publications

Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy

Golgi localized β1-adrenergic receptors stimulate Golgi PI4P hydrolysis by PLCε to regulate cardiac hypertrophy

Autocrine Bradykinin Release Promotes Ischemic Preconditioning-Induced Cytoprotection in Bovine Aortic Endothelial Cells

Platelet Proteome Changes in Dogs with Chronic Heart Failure

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