Abstract
Erectile function is regulated by complex mechanisms centered on vascular- and nerve-related systems. Hence, dysregulation of these systems leads to erectile dysfunction (ED), which causes mental distress and decreases the quality of life of patients and their partners. At the molecular level, many factors, such as fibrosis, lipid metabolism abnormalities, the immune system, and stem cells, play crucial roles in the etiology and development of ED. Although phosphodiesterase type 5 (PDE5) inhibitors are currently the standard treatment agents for patients with ED, they are effective only in a subgroup of patients. Therefore, further insight into the pathological mechanism underlying ED is needed to discuss ED treatment strategies. In this review, we focused on the biological and pathological significance of macrophages in ED because the interaction of macrophages with ED-related mechanisms have not been well explored, despite their important roles in vasculogenic and neurogenic diseases. Furthermore, we examined the pathological significance of macrophages in Peyronie’s disease (PD), a cause of ED characterized by penile deformation (visible curvature) during erection and pain. Although microinjury and the subsequent abnormal healing process of the tunica albuginea are known to be important processes in this disease, the detailed etiology and pathophysiology of PD are not fully understood. This is the first review on the pathological role of macrophages in PD.
Highlights
Erectile response in males is suggested to be a series of five phases: latent, tumescent, full erection, rigid erection, and detumescent [1]
A previous study reported that a high-fat diet increased TNF-α levels in the serum and corpus cavernosum of wild-type mice; such changes were not found in toll-like receptor (TLR)9 mutant mice [55]
The results of the study suggested that obesity induced by a high-fat diet led to systemic inflammation and increased the expression of TNF-α in the corpus cavernosum, which was in part mediated by the activation of TLR9 expressed in macrophages [55]
Summary
Erectile response in males is suggested to be a series of five phases: latent, tumescent, full erection, rigid erection, and detumescent [1]. Increased cGMP activates cGMP-dependent protein kinase (PKG), and the subsequent phosphorylation of various proteins, resulting in decreased intracellular calcium levels and a consequent relaxation of smooth muscles, leading to penile erection [2,3]. In addition to these factors, biomolecular activities, such as prostaglandins and oxidative stress, play important roles in the cGMP-related pathway in erectile function [1,4]. The level of cGMP in smooth muscle cells plays a crucial role in penile erection, which is regulated by the balance between cGMP synthesis by guanyl cyclase and cGMP hydrolysis by PDE5 [2,3,6]. We discuss the pharmacological effects of macrophages in the treatment of ED
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