GRK2 Targeted Knock-down Results in Spontaneous Hypertension, and Altered Vascular GPCR Signaling

Tutunea-Fatan, Elena; Caetano, Fabiana A.; Gros, Robert; Ferguson, Stephen S. G.

doi:10.1074/jbc.m114.615658

Cited by 24 publications

(21 citation statements)

References 40 publications

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“…Tutunea-Fatan et al . revealed that genetic knockdown of GRK2 using a small hairpin RNA in mice caused spontaneous hypertension between 8 and 12 weeks of age9. However, the physiological effects of GRKs in hypertension are complicated, and there are differing reports.…”

Section: Discussionmentioning

confidence: 99%

“…G-protein-coupled receptor kinases (GRKs) contain seven members, which have multiple physiological effects in hypertension910. Preliminary experiments and the study by Tiruppathi et al .…”

mentioning

confidence: 99%

“…showed that GRK2, GRK5, and GRK6 were expressed predominantly in ECs11. Although numerous studies have demonstrated the relation between GRK2/5 and hypertension912, the roles of GRK6 in hypertension have not yet been fully elucidated13. Changes in GRK6 have been reported to participate in the functional regulation of various cells.…”

mentioning

confidence: 99%

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Secreted miR-27a Induced by Cyclic Stretch Modulates the Proliferation of Endothelial Cells in Hypertension via GRK6

Wang

Bao

Wang

et al. 2017

Sci Rep

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Abnormal proliferation of endothelial cells (ECs) is important in vascular remodeling during hypertension, but the mechanisms are still unclear. In hypertensive rats caused by abdominal aortic coarctation, the expression of G-protein-coupled receptor kinase 6 (GRK6) in ECs at common carotid artery was repressed in vivo, and EC proliferation was increased. 15% cyclic stretch in vitro, which mimics the pathologically increased stretch in hypertension, repressed EC GRK6 expression via paracrine control by vascular smooth muscle cells (VSMCs). Furthermore, VSMC-derived microparticles (VSMC-MPs) were detected in the conditioned medium from VSMCs and in artery. VSMC-MPs from cells exposed to 15% cyclic stretch decreased GRK6 expression and increased EC proliferation. miR-27a was detected in VSMC-MPs and was upregulated by 15% cyclic stretch. miR-27a was transferred from VSMCs to ECs via VSMC-MPs and directly targeted on GRK6. Finally, a multi-point injection of antagomiR-27a around carotid artery decreased miR-27a expression in vivo, induced GRK6 expression, and reversed the abnormal EC proliferation. Pathologically elevated cyclic stretch increased the secretion of miR-27a, which was transferred from VSMCs to ECs via the VSMC-MPs, subsequently targeted GRK6, and induced EC proliferation. Locally decreasing miR-27a could be a novel therapeutic approach to attenuate the abnormal EC proliferation in hypertension.

show abstract

Section: Discussionmentioning

confidence: 99%

“…G-protein-coupled receptor kinases (GRKs) contain seven members, which have multiple physiological effects in hypertension910. Preliminary experiments and the study by Tiruppathi et al .…”

mentioning

confidence: 99%

See 1 more Smart Citation

Secreted miR-27a Induced by Cyclic Stretch Modulates the Proliferation of Endothelial Cells in Hypertension via GRK6

Wang

Bao

Wang

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…By contrast, other GRKs (GRK2, GRK3, GRK5, and GRK6) are expressed ubiquitously throughout the body. Accordingly, except for GRK1 and GRK7, other GRK members (GRK2–6) exert different physiological effects, specifically, the regulation of blood pressure by the cardiovascular system and the kidney …”

Section: Role Of Grks In the Regulation Of Blood Pressurementioning

confidence: 99%

“…A role of GRK2 in the regulation of blood pressure has been shown in animal models with partial germline deletion, universal GRK2 knockdown, and targeted overexpression or knockdown in vascular smooth muscle and endothelial cells . GRK2 plays an important role in the regulation of blood pressure .…”

Section: Role Of Grks In the Regulation Of Blood Pressurementioning

confidence: 99%