Mechanisms of Penile Fibrosis

Abstract

Penile fibrosis has been conceptually identified with the plaque that develops in the tunica albuginea in Peyronie's disease (PD), or with localized processes induced in the corpora cavernosa by ischemic or traumatic events. Recently, it has been proposed that a diffuse, progressive, and milder intracorporal fibrosis, which affects also the media of the penile arteries, is responsible for vasculogenic erectile dysfunction (ED) associated with aging, smoking, diabetes, hypertension, and post-radical prostatectomy. These processes differ in etiology, time course, target cells, and treatment, but have many features in common. To review the literature pertaining to fibrosis in the penis, related to PD and ED. PubMed search for pertinent publications mainly during 2001-2008. This review focuses initially on PD and then deals with studies on ED in animal and cell culture models, discussing some of the pathophysiological similarities between tunical fibrosis in PD and corporal fibrosis in corporal veno-occlusive dysfunction (CVOD), and emerging therapeutic strategies. The role of profibrotic factors, the excessive deposit of collagen fibers and other extracellular matrix, the appearance of a synthetic cell phenotype in smooth muscle cells or the onset of a fibroblast-myofibroblast transition, and in the case of the corporal or penile arterial tissue the reduction of the smooth muscle cellular compartment, are discussed. This histopathology leads either to localized plaques or nodules in penile tissues, or to the diffuse fibrosis causing impairment of tissue compliance that underlies CVOD and arteriogenic ED. The antifibrotic role of the sustained stimulation of the nitric oxide/cyclic guanosine monophosphate pathway in the penis and its possible relevance to exogenous and endogenous stem cell differentiation is also briefly presented. Fibrotic processes in penile tissues share a similar cellular and molecular pathophysiology and common endogenous mechanisms of defense that have inspired novel pharmacological experimental approaches.