Cyclosporine A induces vascular fibrosis and heat shock protein expression in rat

The immunosuppressive drug Cyclosporine A (CsA) has been successfully used in several diseases with immunological basis and in transplant patients. However, the therapeutic treatment induces several side effects, which include the development of severe hypertension, renal failure and cardiotoxicity in the majority of the patients. Since the mechanism by which CsA induces hypertension is not well defined, the aim of this study is to evaluate the morphological changes and the expression of heat shock proteins (HSPs) in the thoracic aorta of CsA-treated rats. The study was carried out on 40 male Wistar rats with an average weight of 200-250 g. The animals were divided into four groups. Groups I and II were injected subcutaneously (sc) daily with castor oil for 15 or 30 days and used as control; group III and IV were injected sc daily with CsA (15 mg/Kg/day) for 15 or 30 days. After the end of the treatment, the thoracic aortae were removed and treated for morphological (Sirius Red) and immunohistochemical evaluation (HSP 25, alphaB-crystallin and HSP 47). The results indicate that CsA induces (1) time-dependent vascular damage visible as fibrosis mainly in intima-media tunica of aorta, and (2) a clear increase in HSP expression. In fact, after 30 days of treatment, HSP and alphaB-crystallin are increased in all tunicas, whereas HSP47 only in tunica media and adventitia. These findings could suggest that these proteins are up-regulated after CsA treatment in order to play a defensive role in vascular damage.