Dataset Information

Molecular and Histologic Evidence of Novel Erectile Dysfunction Rat Model as an Aging Atherosclerosis Model: A Preliminary Study.

ABSTRACT:

Purpose

To validate a novel arteriogenic erectile dysfunction (ED) model with atherosclerosis (AS) based on molecular and histologic evidence induced by chronic pelvic ischemia (CPI) and determine effect of phosphodiesterase-5 inhibitor treatment.

Materials and methods

Twenty 16-week-old male Sprague-Dawley rats were divided into three experimental groups (Group I, untreated sham-operated rats with regular diet; Group II, CPI with cholesterol diet; Group III, CPI model with cholesterol diet and mirodenafil). Erectile function was accessed using maximum intracavernous pressure (ICP) and ICP/mean arterial pressure (MAP). Molecular changes were examined by western blot analysis using hypoxia inducible factor 1-alpha (HIF-1α), endothelial nitric oxide synthase (eNOS), and transforming growth factor beta-1 (TGF-β1) antibodies. Collagen change was evaluated by Masson's trichrome staining.

Results

In vivo measurements of ICP and ICP/MAP in Group II were significantly lower than those in Group I (p<0.01). Smooth muscle/collagen ratio in Group II was significantly lower than that in Group I (p<0.05). After treatment with mirodenafil for four weeks, Group III showed significantly higher levels of ICP and ICP/MAP than Group II (p<0.05). Western blot analysis showed that HIF-1α and TGF-β1 levels were significantly higher in Group II whereas eNOS levels were significantly lower in Group II than those in Group I or III.

Conclusions

A novel arteriogenic ED with AS model is successfully induced by CPI and validated based on molecular and histologic evidences.

SUBMITTER: Kim JH

PROVIDER: S-EPMC7308229 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Molecular and Histologic Evidence of Novel Erectile Dysfunction Rat Model as an Aging Atherosclerosis Model: A Preliminary Study.

Kim Jae Heon JH Shim Ji Sung JS Kim Jong Wook JW Doo Seung Whan SW Bae Jae Hyun JH Lee Ju Han JH Song Yun Seob YS Kim Je Jong JJ Moon Du Geon DG

The world journal of men's health 20190614 3

<h4>Purpose</h4>To validate a novel arteriogenic erectile dysfunction (ED) model with atherosclerosis (AS) based on molecular and histologic evidence induced by chronic pelvic ischemia (CPI) and determine effect of phosphodiesterase-5 inhibitor treatment.<h4>Materials and methods</h4>Twenty 16-week-old male Sprague-Dawley rats were divided into three experimental groups (Group I, untreated sham-operated rats with regular diet; Group II, CPI with cholesterol diet; Group III, CPI model with choles ...[more]

PMID: 31385467

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Project description:ObjectivesTo investigate the feasibility of the Zucker fatty (ZF) rat as a model for research in to obesity-associated erectile dysfunction (OAED) and to determine the effect of low-intensity extracorporeal shockwave therapy (Li-ESWT) on penile tissue and function in these rats.Materials and methodsEight new-born male Zucker lean (ZL group) rats (ZUC-Leprfa 186) and 16 new-born male ZF rats (ZUC-Leprfa 185) were injected with 5-ethynyl-2'-deoxyuridine (EdU) at birth to identify and monitor endogenous stem cells. Insulin tolerance testing was performed at 10 weeks of age. Beginning at 12 weeks of age, eight ZF rats were kept as controls, and the remaining eight ZF rats were treated with Li-ESWT (0.02 mJ/mm2 , 3 Hz, 500 pulses; ZF + SW group) twice a week for 4 weeks. Following a 1-week washout period, erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). Penile tissues were then harvested for histological study to assess smooth muscle/collagen content and endothelium content in the corpora cavernosum. LipidTOX™ staining was used to evaluate lipid accumulation. EdU, as a marker of cell activation, and phosphorylated histone 3 (H3P), as a marker of cell mitosis, were also assessed.ResultsThe ICP/MAP indicated that erectile function was severely impaired in the ZF group as compared with the ZL group. In the ZF + SW group, erectile function was significantly improved (P < 0.05). Muscle atrophy was seen in the ZF group, while Li-ESWT increased the muscle content in ZF + SW group. Moreover, the penile endothelium was damaged in the ZF group, and Li-ESWT enhanced the regeneration of endothelial cells (P < 0.01) in the ZF + SW group. Lipid accumulation was seen in the penile tissue of ZF rats. Li-ESWT significantly reduced both the amount and the distribution pattern of LipidTOX, suggesting decreased overall lipid infiltration. Furthermore, Li-ESWT increased EdU-positive cells and markedly enhanced the phosphorylation level of H3P at Ser-10 in the ZF + SW group. Most H3P-positive cells were located within smooth muscle cells, with some located in the endothelium suggesting that these tissues are the reservoirs of penile stem/progenitor cells.ConclusionZF rats can serve as an animal model in which to study OAED. This study reveals that obesity impairs erectile function by causing smooth muscle atrophy, endothelial dysfunction, and lipid accumulation in the corpus cavernosum. Li-ESWT restored penile haemodynamic parameters in the ZF rats by restoring smooth muscle and endothelium content and reducing lipid accumulation. The underlying mechanism of Li-ESWT appears to be activation of stem/progenitor cells, which prompts cellular proliferation and accelerates penile tissue regeneration. Our findings are of interest, not just as a validation of this emerging treatment for erectile dysfunction, but also as a novel and potentially significant method to modulate endogenous stem/progenitor cells in other disease processes.

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Project description:Protein expression profiles in rat corporal smooth muscle tissue were compared between animal models of streptozotocin-induced diabetes mellitus (STZ-DM) and age-matched controls (AMCs) at 1 week and 2 months after induction of hyperglycemia with STZ treatment. At each time point, protein samples from four STZ-DM and four AMC rat corpora tissues were prepared independently and analyzed together across multiple quantitative two-dimensional gels using a pooled internal standard sample to quantify expression changes with statistical confidence. A total of 170 spots were differential expressed among the four experimental groups. A subsequent mass spectrometry analysis of the 170 spots identified a total of 57 unique proteins. Network analysis of these proteins using MetaCore suggested altered activity of transcriptional factors that are of too low abundance to be detected by the two-dimensional gel method. The proteins that were down-regulated with diabetes include isoforms of collagen that are precursors to fibril-forming collagen type 1; Hsp47, which assists and mediates the proper folding of procollagen; and several proteins whose abundance is controlled by sex hormones (e.g. CRP1 and A2U). On the other hand, proteins seen or predicted to be up-regulated include proteins involved in cell apoptosis (e.g. p53, 14-3-3-gamma, Serpinf1, Cct4, Cct5, and Sepina3n), proteins that neutralize the biological activity of nerve growth factor (e.g. anti-NGF 30), and proteins involved in lipid metabolism (e.g. apoA-I and apoA-IV). Subsequent Western blot validation analysis of p53, 14-3-3-gamma, and Hsp47 confirmed increased p53 and 14-3-3-gamma and decreased Hsp47 levels in separate samples. According to the results from the Western blot analysis, Hsp47 protein showed a approximately 3-fold decrease at 1 week and was virtually undetectable at 2 months in diabetic versus control. Taken together, our results identify novel candidate proteins playing a role in erectile dysfunction in diabetes resulting from STZ treatment.

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Dataset Information

Molecular and Histologic Evidence of Novel Erectile Dysfunction Rat Model as an Aging Atherosclerosis Model: A Preliminary Study.

Purpose

Materials and methods

Results

Conclusions

Publications

Molecular and Histologic Evidence of Novel Erectile Dysfunction Rat Model as an Aging Atherosclerosis Model: A Preliminary Study.

Similar Datasets

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