Amelioration of Penile Fibrosis: Myth or Reality

Abstract

Several changes have been reported to occur in the cavernosal tissue and tunica albuginea with aging. The atherosclerosis of the penis that occurs with aging causes a decrease in penile oxygen tension. A reduction in the number of smooth muscle cells (SMCs) has been demonstrated in relation to this change in oxygen tension. Changes in the ratio of penile collagen have also been observed and could explain the decrease in penile elasticity and compliance with aging. Chronic ischemia is therefore associated with fibrosis but also with nitric oxide-cGMP reduction. The sensitivity of the a-adrenoceptors on the SMCs increases with aging. Furthermore, androgen deprivation produces penile tissue atrophy, alterations in dorsal nerve structure, alterations in endothelial morphology, reductions in trabecular SM content, increases in deposition of extracellular matrix, and increases in accumulation of adipocytes in the subtunical region of the corpus cavernosum. All of these modifications can explain the prevalence of erectile dysfunction with aging. The aim of this review is to address the underlying etiology of corporal fibrosis, especially aging, cavernosal nerve damage, androgen deprivation, and tunical fibrosis. Finally, we will address the proposed amelioration and reversal of fibrosis in terms of correcting, at least partially, the relative SMC loss that occurs with aging, diabetes, or cavernosal nerve damage and its impact on prevention of erectile dysfunction-associated cavernosal fibrosis.

Losartan Preserves Erectile Function by Suppression of Apoptosis and Fibrosis of Corpus Cavernosum and Corporal Veno-Occlusive Dysfunction in Diabetic Rats

“…Activation of Smad- and non-Smad-dependent TGF-β1 signaling pathways is believed to contribute to Ang II-induced apoptosis and tissue fibrosis [14, 15, 40, 43, 44]. It was previously reported that treatment with losartan suppressed the TGF-β1/Smad pathway and preserved erectile function [7, 21]. However, these results did not predict whether Ang II antagonism would attenuate apoptosis and fibrosis in the corpus cavernosum and severe CVOD.…”

“…CVOD is the inability of the corporal smooth muscle mass to relax sufficiently, which results in inadequate compression of the subtunical veins, a concomitant inability to retain blood within the corpora, and, thus, incomplete tumescence. Therefore, any process that damages the structure and/or function of the corpus cavernosum, such as reduced smooth muscle content and increased collagen deposition, or ultimately corporal fibrosis, will predispose an individual to developing CVOD [7]. Numerous studies have demonstrated that apoptosis plays a critical role in fibrosis in different organs such as the liver, lungs, kidneys, heart, and penile corpora cavernosa [7-10].…”

“…Therefore, any process that damages the structure and/or function of the corpus cavernosum, such as reduced smooth muscle content and increased collagen deposition, or ultimately corporal fibrosis, will predispose an individual to developing CVOD [7]. Numerous studies have demonstrated that apoptosis plays a critical role in fibrosis in different organs such as the liver, lungs, kidneys, heart, and penile corpora cavernosa [7-10]. Both animal and human studies have demonstrated that angiotensin II (Ang II) is critically involved in promoting apoptosis, collagen deposition, and tissue fibrosis through various mechanisms [10-14].…”

Androgen depletion in humans leads to cavernous tissue reorganization and upregulation of Sirt1–eNOS axis

“…The nucleus is stained blue (DAPI). Negative controls were performed by primary antibody omission (d, h) Aging also leads to change of the cavernous tissue structure (Ferrer et al 2010;Luo et al 2007;Tomada et al 2008Tomada et al , 2010bWespes et al 1991) and, despite the controversy of reports concerning SM and CT content, such changes seem to be one of multiple contributing factors for the age-dependent erectile dysfunction (El-Sakka and Yassin 2010;Yassin and Saad 2008).…”

The Old Made New: Natural Compounds against Erectile Dysfunction

“…In particular, the prevalence of ED rises in aging subjects as a result, primarily, of a progressive worsening of conditions influencing erectile biology [13]. Briefly, in the aging male, the vascular supply to the penis becomes defective due to atherosclerotic alterations [14]. In addition, a reduced response to contraction-relaxation stimuli is enlightened, in particular due to the modulation of the expression of a 1 receptors in the human prostatic, bladder, and erectile tissues [15] or the compromised nitric oxide (NO) production by penile endothelium that leads to a reduced NO plasmatic level [16].…”