Abstract: PD31-11
Sources of Funding: R01 DK10509701 (TL); R21 DK109912 (SPH, MLS); R01 DE022032 (SPH)

Introduction

Calcified Peyronie's plaque (CPP) is thought to be mineralized type I collagen of the tunica albuginea (TA) and within the corpus cavernosum (CC). The mechanistic link transforming a fibrous and vascularized to a mineralized tissue and subsequently impairing function at an organ-level is poorly understood. It is hypothesized that origins of CPP lay at the interface between the circumferential TA and CC, in that the residing pericytes around small diameter vessels produce osteogenic markers, prompting calcification at the CC-TA interface. _x000D_

Methods

Twelve human CPPs were surgically excised, fixed, dehydrated and scanned using a high resolution X-ray computed tomography (micro-CT) at 4X and 10X magnifications (4.5µm and 1.8µm voxel size respectively) and further analyzed with AVIZO for mineral density, porosity and structure. Tissues were processed and stained histologically, and imaged using an Olympus BX51 microscope. _x000D_

Results

CPP contained pores (A) with a diameter range of 10-18µm (A, C), see figure. Micro-CT data demonstrated an interface with a lower mineral density of 765 ±172mg/cc between layers 1 and 2 (A in figure) compared to the average mineral density of 1049 ±142mg/cc. Interfacial zone between TA and CC contained tubules of diameter 18±3.5µm with mineralized lumen walls (A). Histological analyses of seemingly non-calcified regions adjacent to CPP, contained similar diameter tubules patent with erythrocytes (region 1 in B in figure), and were within a disorganized extracellular matrix (ECM) positive for increased expression of elastin (bottom row, elastin) within regions positive for alizarin red (bottom row, AR: mineral). These patterns were consistently observed at the interface between TA and CC regions. _x000D_

Conclusions

The branch-like structure of 10-18µm pores is similar to that of the venous structure at the interface between the TA and CC, suggesting that cells within and around the small diameter vessel could play a role in biomineralization, likely following an insult on the outer layers of the TA. Increased expression of elastin alters ECM stiffness within the outer TA prompting a change in smooth muscle stiffness of the CC, and collectively over time can receive signals from the interface to accelerate biomineralization along the length of the penis._x000D_

Funding

R01 DK10509701 (TL); R21 DK109912 (SPH, MLS); R01 DE022032 (SPH)