Salt intake and blood pressure response to percutaneous renal denervation in resistant hypertension

The effect of lowering sympathetic nerve activity by renal denervation (RDN) is highly variable. With the exception of office systolic blood pressure (BP), predictors of the BP-lowering effect have not been identified. Because dietary sodium intake influences sympathetic drive, and, conversely, sympathetic activity influences salt sensitivity in hypertension, we investigated 24-hour urinary sodium excretion in participants of the SYMPATHY trial. SYMPATHY investigated RDN in patients with resistant hypertension. Both 24-hour ambulatory and office BP measurements were end points. No relationship was found for baseline sodium excretion and change in BP 6 months after RDN in multivariable-adjusted regression analysis. Change in the salt intake–measured BP relationships at 6 months vs baseline was used as a measure for salt sensitivity. BP was 8 mm Hg lower with similar salt intake after RDN, suggesting a decrease in salt sensitivity. However, the change was similar in the control group, and thus not attributable to RDN

TWEAK, via its receptor Fn14, is a novel regulator of mesenchymal progenitor cells and skeletal muscle regeneration

Inflammation participates in tissue repair through multiple mechanisms including directly regulating the cell fate of resident progenitor cells critical for successful regeneration. Upon surveying target cell types of the TNF ligand TWEAK, we observed that TWEAK binds to all progenitor cells of the mesenchymal lineage and induces NF-κB activation and the expression of pro-survival, pro-proliferative and homing receptor genes in the mesenchymal stem cells, suggesting that this pro-inflammatory cytokine may play an important role in controlling progenitor cell biology. We explored this potential using both the established C2C12 cell line and primary mouse muscle myoblasts, and demonstrated that TWEAK promoted their proliferation and inhibited their terminal differentiation. By generating mice deficient in the TWEAK receptor Fn14, we further showed that Fn14-deficient primary myoblasts displayed significantly reduced proliferative capacity and altered myotube formation. Following cardiotoxin injection, a known trigger for satellite cell-driven skeletal muscle regeneration, Fn14-deficient mice exhibited reduced inflammatory response and delayed muscle fiber regeneration compared with wild-type mice. These results indicate that the TWEAK/Fn14 pathway is a novel regulator of skeletal muscle precursor cells and illustrate an important mechanism by which inflammatory cytokines influence tissue regeneration and repair. Coupled with our recent demonstration that TWEAK potentiates liver progenitor cell proliferation, the expression of Fn14 on all mesenchymal lineage progenitor cells supports a broad involvement of this pathway in other tissue injury and disease settings