The association between local atherosclerosis of the prostatic artery and benign prostatic enlargement in humans: Putative mechanism of chronic ischemia for prostatic enlargement

Prostate. 2018 Sep;78(13):1001-1012. doi: 10.1002/pros.23658. Epub 2018 May 21.

Abstract

Background: To investigate the possible pathogenesis of the benign prostatic enlargement (BPE) induced by local atherosclerosis, the association between local atherosclerosis and prostatic enlargement was investigated, and molecular biological analyses were performed using human prostatectomy specimens.

Methods: A total of 69 consecutive patients who underwent robot-assisted radical prostatectomy (RARP) participated in this prospective study. To evaluate actual local atherosclerosis, prostatic arteries were removed during RARP. Microscopic assessment of local atherosclerosis was classified as one of three degrees of narrowing (minimal, moderate, and severe) according to the degree of obstruction of the inner cavity of the prostatic artery. The expressions of several mediators related to chronic ischemia and cell proliferation of the prostate were investigated by immunohistochemistry.

Results: The median age of the present cohort was 68 (range: 55-75) years. Although there was no relationship between local atherosclerosis and lower urinary symptoms evaluated by questionnaires, local atherosclerosis was significantly more severe in patients who had a history of treatment for benign prostatic hyperplasia (P = 0.02). Prostate size was significantly larger in the severe local atherosclerosis group than in the minimal and moderate local atherosclerosis groups (P < 0.001 and P = 0.03, respectively). Thepositive expression rates of hypoxia-inducible factor (HIF)-1α, malondialdehyde (MDA), transforming growth factor (TGF)-β1 , and basic fibroblast growth factor (bFGF) in the prostate were significantly higher in patients with local atherosclerosis than in patients without local atherosclerosis (all P < 0.01, respectively).

Conclusions: In human surgical specimens, there is evidence that local atherosclerosis of the prostatic artery is significantly associated with prostate size. Given the molecular evidence provided in this study, the putative mechanism for this relationship is that chronic ischemia induced upregulation of oxidative stress pathways, leading to BPE.

Keywords: benign prostatic hyperplasia; human; lower urinary tract; lower urinary tract symptoms; radical prostatectomy.

MeSH terms

  • Aged
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology*
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Ischemia / metabolism
  • Ischemia / pathology*
  • Lower Urinary Tract Symptoms / metabolism
  • Lower Urinary Tract Symptoms / pathology*
  • Male
  • Malondialdehyde / metabolism
  • Middle Aged
  • Prostate / blood supply*
  • Prostate / metabolism
  • Prostate / pathology
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Transforming Growth Factor beta1
  • Fibroblast Growth Factor 2
  • Malondialdehyde