fibrin and Penile-Induration

Peyronie's disease is characterized by local fibrosis of the tunica albuginea and relatively rare clinically. Few relevant basic researches could be retrieved, which might be attributed to the absence of a robust animal model of the disease as well as to its rareness. At present, some animal models available for Peyronie's disease have their own merits and demerits. TGF-β1-induced and Fibrin-induced models are lack of penile curvature and calcification/ossification. A surgical model might be established for the acute phase of the disease. The characteristic of a widespread fibrotic process involving many organs in the spontaneous model is quite different from that of human Peyronie's disease. Therefore, choosing the right model is essential for researches. This paper presents an overview of the animal models of Peyronie's disease, meant to provide some reference for the basic research of the disease.

Topics: Animals; Disease Models, Animal; Fibrin; Fibrosis; Humans; Male; Penile Induration; Penis; Transforming Growth Factor beta1

To investigate the role of fibrin in inducing fibrosis in the tunica albuginea (TA) of the rat penis, to develop a new animal model for Peyronie's disease (PD).. The TA of rats (five per group per period) were injected with either saline, fibrin, transforming growth factor-beta1 (TGF-beta1) or TGF-beta1 plus fibrin; the rats were killed at 1, 3, and 6 weeks after injection. Images were analysed quantitatively from tissue sections stained for collagen (Masson trichrome), fibrin (Verhoeff's stain) and elastin (Hart's stain), and immunostained for TGF-beta1, inducible nitric oxide synthase (iNOS), heme oxygenase 1 (HO1), alpha-smooth muscle actin (ASMA), apoptosis (TUNEL) and plasminogen activator inhibitor (PAI). Collagen fibre organization was characterized by electron microscopy. Human PD plaque tissue and normal human TA were assayed for fibrin by immunohistochemistry in nine samples.. At 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 TGF-beta1 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-beta1 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-beta1 groups persisted, and were comparable with those elicited at this time by TGF-beta1 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-beta1 than the TA of the animals receiving TGF-beta1 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.. These 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-beta1, and induces a plaque not only histologically similar to that induced by TGF-beta1 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.

Topics: Animals; Disease Models, Animal; Fibrin; Fibrosis; Humans; Immunohistochemistry; Male; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Penile Induration; Penis; Rats; Rats, Sprague-Dawley; Transforming Growth Factor beta

The extracellular matrix that is present at sites of tissue repair in most instances undergoes an orderly transition from a fibrin containing matrix to collagen-rich scar. However, in some conditions, such as Peyronie's disease, fibrin persists. Evidence from a number of experimental systems indicates that extracellular matrix proteins and their receptors serve an important function in regulating cell behaviors. Thus, the presence of the fibrin matrix is likely to have important implications in the course of either normal or pathogenic wound healing as occurs in Peyronie's disease. Potential mechanisms by which the fibrin rich provisional matrix appears in healing wounds are presented.. Methodologies, such as in situ hybridization, immunolocalization and labeled tracer techniques, were used in our study.. We found by these approaches that the 2 general mechanisms that contribute to the generation of the wound extracellular matrix are leakage of plasma proteins, such as plasma fibronectin and fibrinogen, and the synthesis of variants of fibronectin by wound cells.. Developing an understanding of the mechanisms that regulate the appearance of these matrix proteins may provide new avenues for therapy in conditions such as Peyronie's disease in which the temporal pattern of the provisional matrix deposition is abnormal.

Topics: Animals; Endothelial Growth Factors; Extracellular Matrix; Fibrin; Fibronectins; Lymphokines; Male; Penile Induration; Rodentia; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors; Wound Healing

Peyronie's disease is a pathological fibrosis characterized by excessive deposition of collagen in the plaque. Although the etiology of Peyronie's disease is unknown, trauma has been hypothesized as the inciting event. In an effort to obtain more insight into the pathogenesis of Peyronie's disease plaque tissue was examined for collagen, elastic fiber, and fibrin content and distribution.. Plaque tissue specimens from 33 patients with Peyronie's disease, control penile tissue and nodular tissue from 8 patients with Dupuytren's contracture were analyzed histochemically for collagen staining and elastic fiber structure and distribution. Plaque tissue from 19 Peyronie's disease patients, control tissue and nodular tissue from Dupuytren's disease were also analyzed for the presence of fibrin by histochemical staining and immunoblotting.. Aberrantly stained collagen was detected in 32 of 33 plaque specimens (97%) and disrupted elastic fibers in 31 of the same specimens (94%). Fibrin deposition was detected histochemically in plaque tissue from 18 of 19 patients (95%) but it was not detectable in normal or scarred tunica from control patients. The presence of authentic fibrin accumulation in plaque tissue was confirmed by immunoblot analysis but fibrin was not detected in dermal tissue extracts from the same patient. Aberrant collagen staining and fibrin deposition were detected in nodular tissue from 7 of 8 Dupuytren's contracture patients (88%) and altered elastic fibers in 5 of the same patients (63%).. Deposition of fibrin in plaque tissue is consistent with the hypothesis that repetitive microvascular injury results in fibrin deposition in the tissue space and has served to provide insights into the pathophysiology of Peyronie's disease. We propose a model that accounts for the clinical and biological features of Peyronie's disease.

Topics: Adult; Aged; Collagen; Elastin; Fibrin; Fibrosis; Humans; Male; Middle Aged; Penile Induration