SGK1 may play an important role in macrophage recruitment and M2 macrophage activation by activating the STAT3 pathway, which leads to angiotensin II-induced cardiac fibrosis.

Mutations in the transcription factor FOXC2 are predominately associated with lymphedema. Herein, we demonstrate a key role for related factor FOXC1, in addition to FOXC2, in regulating cytoskeletal activity in lymphatic valves. FOXC1 is induced by laminar, but not oscillatory, shear and inducible, endothelial-specific deletion impaired postnatal lymphatic valve maturation in mice. However, deletion of Foxc2 induced valve degeneration, which is exacerbated in Foxc1; Foxc2 mutants. FOXC1 knockdown (KD) in human lymphatic endothelial cells increased focal adhesions and actin stress fibers whereas FOXC2-KD increased focal adherens and disrupted cell junctions, mediated by increased ROCK activation. ROCK inhibition rescued cytoskeletal or junctional integrity changes induced by inactivation of FOXC1 and FOXC2 invitro and vivo respectively, but only ameliorated valve degeneration in Foxc2 mutants. These results identify both FOXC1 and FOXC2 as mediators of mechanotransduction in the postnatal lymphatic vasculature and posit cytoskeletal signaling as a therapeutic target in lymphatic pathologies.

Hypertension is one of the major risk factors for cardiovascular disease, with an impact on global health. Multiple studies have suggested that various dietary factors are associated with blood pressure (BP) and hypertension. The purpose of this Review is to provide up-to-date knowledge on the impact of dietary factors on BP and hypertension, to compare types and recommended intakes of dietary factors in hypertension management and prevention guidelines from different countries and organizations, and to outline global population-based healthy-diet strategies for hypertension control. Of the 27 dietary factors we evaluated on the basis of specified review criteria, 17 have been proposed to have protective effects against hypertension, six were proposed to be risk factors for hypertension, and the association between BP and the remaining factors was considered inconclusive. Excessive sodium intake is a causal risk factor for hypertension, whereas a diet rich in fruit, vegetables, and low-fat dairy products, and low in sodium and saturated fat has been recommended to prevent and reduce hypertension on the basis of strong evidence. Notable differences exist in the recommended types and intakes of dietary factors among available hypertension management and prevention guidelines. Available evidence supports the vigorous implementation of dietary strategies against hypertension through population-based, national action plans.