Fibrin as an inducer of fibrosis in the tunica albuginea of the rat: a new animal model of Peyronie's disease

Abstract

RESULTSAt 1 week after injection of fibrin into the rat TA, only oedema was present; at 3 weeks, the oedema developed into a characteristic fibrotic PD-like plaque. The injection of TGFb 1 into the TA also induced oedema in the TA at 1 and 3 weeks but there was very little evidence of a recognisable plaque at either time. Injection with TGF-b 1 plus fibrin resulted in oedema at 1 week but at 3 weeks there was a smaller plaque than with fibrin only. At 6 weeks the induced plaques in the fibrin-only and fibrin + TGF-b 1 groups persisted, and were comparable with those elicited at this time by TGF-b 1 alone. The control animals showed no pathology at any of the sample times. At 3 weeks the PD plaque induced by injection with fibrin alone had not only greater expression of TGF-b 1 than the TA of the animals receiving TGF-b 1 alone, but also greater levels of other markers of fibrosis, e.g. HO1 (reactive oxygen species), ASMA (presence of myofibroblasts), apoptosis, and PAI (inhibitor of fibrinolysis). iNOS, a known antifibrotic agent, was also increased. In human PD plaque tissue, fibrin was detected by immunohistochemistry in all nine specimens. CONCLUSIONSThese results suggest that fibrin, when introduced into the TA of the rat penis, acts as a potential profibrotic protein, possibly via the local release of TGF-b 1, and induces a plaque not only histologically similar to that induced by TGF-b 1 but to that of the human condition. Because fibrin can extravasate from the blood into the human TA after an injury to the TA, and because fibrin persists in the plaque tissue, we hypothesise that fibrin may play a key role in the pathogenesis of human PD.

Animal experimental model of Peyronie’s disease: A pilot study

“…during sexual activity) can result in delamination of the tunica albuginea and microvascular damage (8,15). Fibrin was found to be potentially involved in the development of the fibrotic plaque in a murine model of PD (16). In the same study, and in another more recent (17), was also reported the presence of increased levels of PAI-1, an important inhibitor of fibrinolysis and collagenolysis: its increased activation appears to play a key role in the development of penile plaque.…”

“…Based on these innovative clinical and histological findings has assumed a possible application of lipofilling technique in patients with PD. It was therefore drawn up an experimental protocol consists of two basic steps: 1. creating an animal model of PD on the basis of experiments already conducted (16,25) have all been taken into account, but basically considered to be associated with erectile dysfunction more than strictly to PD. Microscopically, the tunica albuginea is largely composed by fibrillar collagen type I, woven with elastin fibers, in order to form organized structures (5).…”

“…In a work of Pretorius et al (26) also the PD was studied by magnetic resonance imaging: there was evidence of a thickening of the tunica albuginea, visible in both T2-weighted both in those T1-weighted images. Davila et al (16) have recently proposed an animal model of IPP injecting at the level of the tunica albuginea of rat 30 μ l of fibrin and thrombin, inducing edema after one week after inoculation and fibrosis after three weeks. The use of these components would trigger the final steps of the coagulation cascade and reproduces experimentally what happens after a trauma at the level of the tunica albuginea.…”

A Preliminary Study on Possible Effects of Mitomycin-C on the Collagen Content of Penis in Rat

“…A better knowledge of Peyronie's disease pathogenesis could help us have more treatment options. Therapy options, particularly for the late phase of Peyronie's disease are severely limited [4,5]. No medical treatment that can relieve all symptoms in patients with Peyronie's disease is currently available.…”

“…The primary reason for this and the cause of the PD plaque is unknown and the molecular pathology is poorly understood, although it is thought that often the plaque develops as the result of an abnormal wound healing process after a TA trauma [4][5][6]. Peyronie's disease is characterized by development of a fibrotic plaque [7].…”