The results of our in vitro experiments indicate that exposing cultured human aortic smooth muscle cells and dermal fibroblasts to 39 to 41 °C induces a significant up-regulation in the net deposition of elastic fibers, but not of
collagen I or
fibronectin, and also decreases the deposition of
chondroitin sulfate-containing moieties. We further demonstrate that mild
hyperthermia also rectifies the insufficient elastogenesis notable in cultures of fibroblasts derived from the stretch-marked skin of adult patients and in cultures of dermal fibroblasts from children with
Costello syndrome, which is characterized by the accumulation of
chondroitin 6-sulfate glycosaminoglycans that induce shedding and inactivation of the 67-kDa
elastin-binding protein. We have previously established that this
protein serves as a reusable chaperone for
tropoelastin and that its recycling is essential for the normal deposition of elastic fibers. We now report that
hyperthermia not only inhibits deposition of
chondroitin 6-sulfate moieties and the consequent preservation of
elastin-binding protein molecules but also induces their faster recycling. This, in turn, triggers a more efficient preservation of
tropoelastin, enhancement of its secretion and extracellular assembly into elastic fibers. The presented results encourage using mild
hyperthermia to restore elastic fiber production in damaged adult skin and to enhance elastogenesis in children with genetic elastinopathies.