PULSED ELECTROMAGNETIC FIELDS INCREASE CGMP RELEASE FROM HUMAN ENDOTHELIAL CELLS

摘要

Pulsed electromagnetic fields (PEMF) are used as adjunctivetherapy for delayed-union fractures, chronic wounds and post-operative pain. Mechanism studies have suggested that the calcium/calmodulin (Ca/CaM)-dependent nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) cascade is an important PEMF signal transduction pathway. PEMF affects the synthesis of NO from endothelial NO synthase (eNOS), by modulating Ca~(2+) binding to CaM, potentially affecting the entire tissue repair pathway from angiogenesis, and proliferation to pain and edema reduction. PEMF modulation of the CaM-dependent NO/cGMP pathway has been reported in articular chondrocytes and in a neuronal cell line, wherein NO was evaluated in real time. Both studies used CaM, NOS and cGMP inhibitors. PEMF signals configured to target the same Ca/CaM pathway that increased tendon and wound healing in a rat model by 69% and 59%, respectively (P<0.001). In a double-blind clinical study we reported that the same PEMF signal reduced post-operative pain by 300% at 5 hrs post-op (P<0.001), possibly via CaM-dependent reduction of IL-1β in the wound bed in the same time frame. PEMF increased angiogenesis by 500% (P<0.001) in an arterial loop model in the rat. HUVEC cultures exhibited significantly augmented tubule formation with PEMF through the induction of FGF-2 and PEMF increased neovascularization in diabetic mice by two-fold by a similar mechanism. CaM-dependent NO is an.essential factor in angiogenesis because it modulates cGMP production which orchestrates FGF-2 and VEGF release.. The goal of this study was therefore to quantify the effect of PEMF on. CaM-dependent cGMP in human endothelial cells.