Human GRK4γ142V Variant Promotes Angiotensin II Type I Receptor-Mediated Hypertension via Renal Histone Deacetylase Type 1 Inhibition.

The influence of a single gene on the pathogenesis of essential hypertension may be difficult to ascertain, unless the gene interacts with other genes that are germane to blood pressure regulation. G-protein-coupled receptor kinase type 4 (GRK4) is one such gene. We have reported that the expression of its variant hGRK4γ(142V) in mice results in hypertension because of impaired dopamine D1 receptor.

The Renin-Angiotensin and Renal Dopaminergic Systems Interact in Normotensive Humans.

The renin-angiotensin-aldosterone (RAAS) and renal dopaminergic systems interact to maintain sodium balance. High NaCl intake increases renal synthesis of dopamine and dopaminergic receptor activity, decreasing epithelial sodium transport, whereas sodium deficit activates the RAAS, increasing epithelial sodium transport. We tested the hypothesis that attenuation of the natriuretic effect of dopamine D1-like receptors during salt restriction results in part from increased RAAS activity in seven salt-resistant normotensive adults using a double-blind placebo-controlled balanced crossover design.

Common variants of the G protein-coupled receptor type 4 are associated with human essential hypertension and predict the blood pressure response to angiotensin receptor blockade.

Non-synonymous GRK4 variants, R65L, A142V and A486V, are associated with essential hypertension in diverse populations. This study replicated the association of GRK4 variants, including GRK4(142V), with human essential hypertension in a Japanese population (n=588; hypertensive, n=486 normotensive controls) and determined whether the presence of GRK4 variants predicted the blood pressure (BP) response to angiotensin receptor blockers (ARBs) in patients with essential hypertension. We analyzed 829 patients and compared the response to ARBs between individuals with no GRK4 variants (n=136) and those with variants at one or any of the three loci (n=693).

Extracellular vesicle-mediated transfer of donor genomic DNA to recipient cells is a novel mechanism for genetic influence between cells.

Extracellular vesicles (EVs) carry signals within or at their limiting membranes, providing a mechanism by which cells can exchange more complex information than what was previously thought. In addition to mRNAs and microRNAs, there are DNA fragments in EVs. Solexa sequencing indicated the presence of at least 16434 genomic DNA (gDNA) fragments in the EVs from human plasma.