Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085580 (essential hypertension)
 14,686 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell migration towards a chemotactic stimulus relies on the re-arrangement of the cytoskeleton, which is triggered by activation of small G proteins RhoA, Rac1 and Cdc42, and leads to formation of lamellopodia and actin polymerisation amongst other effects. Here we show that Rac1 is important for CXCR4 induced chemotaxis but not for CCR1/CCR5 induced chemotaxis. For CXCL12-induced migration via CXCR4, breast cancer MCF-7 cells are reliant on Rac1, similarly to THP-1 monocytes and Jurkat T-cells. For CCL3-induced migration via CCR1 and/or CCR5, Rac1 signalling does not regulate cell migration in either suspension or adherent cells. We have confirmed the involvement of Rac1 with the use of a specific Rac1 blocking peptide. We also used a Rac1 inhibitor EHT 1864 and a Rac1-GEF inhibitor NSC23766 to probe the importance of Rac1 in chemotaxis. Both inhibitors did not block CCL3-induced chemotaxis, but they were able to block CXCL12-induced chemotaxis. This confirms that Rac1 activation is not essential for CCL3-induced migration, however NSC23766 might have secondary effects on CXCR4. This small molecule exhibits agonistic features in internalisation and cAMP assays, whereas it acts as an antagonist for CXCR4 in migration and calcium release assays. Our findings strongly suggest that Rac1 activation is not necessary for CCL3 signalling, and reveal that NSC23766 could be a novel CXCR4 receptor ligand.
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PMID:Rac1 plays a role in CXCL12 but not CCL3-induced chemotaxis and Rac1 GEF inhibitor NSC23766 has off target effects on CXCR4. 2905 Sep 86

The aetiology of essential hypertension is complex and involves both environmental and genetic factors. Approximately 30% of the inter-individual variability in blood pressure is genetically determined. It has been shown that numerous vasoconstrictors stimulate RhoA in local populations of vascular SMCs that, in turn, promote localised constriction of arterial blood vessels and elevations in blood pressure. The VAV3 gene encodes for VAV3 protein, a Rho GEF factor. VAV3-AS1 gene, a lncRNA, may regulate VAV3 expression. We performed an observational prospective case-control study, including patients attending in the Vascular Risk Unit from the University Hospital Salamanca for 6 months. A replication study was performed with data from The Kaiser Permanent database of the University of California. The results suggest that T allele of the VAV3 rs7528153 and G allele of the VAV3-AS1 rs11185222 polymorphisms are associated with an increased risk of developing hypertension. We hypothesise that these polymorphisms could modify blood pressure, likely through a modification in the Rho/Rac pathway. Our results suggest that those polymorphisms could be useful genetic markers of susceptibility to suffering hypertension.
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PMID:VAV3 rs7528153 and VAV3-AS1 rs1185222 polymorphisms are associated with an increased risk of developing hypertension. 3254 Apr 12