A mouse model of hypercholesterolemia-induced erectile dysfunction

Donghua Xie, Shelly I. Odronic, Feihua Wu, Anne M. Pippen, Craig F. Donatucci, Brian H. Annex

Research output: Contribution to journalArticle

Abstract

Introduction. Hypercholesterolemia is one of the most important risk factors for the development of erectile dysfunction (ED) in men. Aim. We employed an established mouse model of hypercholesterolemia. Main Outcome Measures. We test for abnormalities in vasoreactivity in corporal tissue and temporally correlated changes in vasoreactivity with alterations in histology and protein expression. Methods. A total of 150 mice were studied. A total of 100 apolipoprotein-E knockout (ApoE-/-) mice were fed a 1.25% cholesterol diet for 2, 4, 8, and 12weeks (N=25/group), while a group of ApoE-/- and wild-type Bl-6 mice were fed a normal diet. The study was terminated, and all mice were harvested at 22 weeks of age for vasoreactivity, histology, and protein studies from corporal tissues. Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo. The contents of endothelial cells, smooth muscle cells, and smooth muscle/collagen ratio were assessed by immunohistochemistry staining or Masson staining. Level of cyclic guanosine monophosphate (cGMP) was detected by enzyme immunoassay assay. Levels of phosphorylated endothelial nitric oxide synthase (p-eNOS)/total eNOS, neuronal nitric oxide synthase (nNOS), and cyclic GMP-dependent kinase (cGK-1) protein were assessed by Western analysis. Results. Abnormalities in endothelium-dependent and endothelium-independent vasoreactivities, endothelial content, smooth muscle/collagen ratio, p-eNOS phosphorylation at Ser1177 only, nNOS, cGMP, and cGK-1 changed with the different durations of the high-cholesterol diet. Conclusions. These data demonstrate that this mouse model is suitable for investigating aspects of hypercholesterolemic ED.

Original languageEnglish (US)
Pages (from-to)898-907
Number of pages10
JournalJournal of Sexual Medicine
Volume4
Issue number4 I
DOIs
StatePublished - Jul 2007
Externally publishedYes

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Erectile Dysfunction
Hypercholesterolemia
Endothelium
Cyclic GMP
Nitric Oxide Synthase Type I
Nitric Oxide Synthase Type III
Apolipoproteins E
Diet
Smooth Muscle
Histology
Collagen
Guanylate Kinases
Cholesterol
Staining and Labeling
Proteins
Enzyme Assays
Immunoenzyme Techniques
Knockout Mice
Smooth Muscle Myocytes
Endothelial Cells

Keywords

  • Endothelium
  • Impotence
  • Nitric oxide synthase
  • Penis
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology
  • Urology

Cite this

A mouse model of hypercholesterolemia-induced erectile dysfunction. / Xie, Donghua; Odronic, Shelly I.; Wu, Feihua; Pippen, Anne M.; Donatucci, Craig F.; Annex, Brian H.

In: Journal of Sexual Medicine, Vol. 4, No. 4 I, 07.2007, p. 898-907.

Research output: Contribution to journalArticle

Xie, Donghua ; Odronic, Shelly I. ; Wu, Feihua ; Pippen, Anne M. ; Donatucci, Craig F. ; Annex, Brian H. / A mouse model of hypercholesterolemia-induced erectile dysfunction. In: Journal of Sexual Medicine. 2007 ; Vol. 4, No. 4 I. pp. 898-907.
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AU - Xie, Donghua

AU - Odronic, Shelly I.

AU - Wu, Feihua

AU - Pippen, Anne M.

AU - Donatucci, Craig F.

AU - Annex, Brian H.

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N2 - Introduction. Hypercholesterolemia is one of the most important risk factors for the development of erectile dysfunction (ED) in men. Aim. We employed an established mouse model of hypercholesterolemia. Main Outcome Measures. We test for abnormalities in vasoreactivity in corporal tissue and temporally correlated changes in vasoreactivity with alterations in histology and protein expression. Methods. A total of 150 mice were studied. A total of 100 apolipoprotein-E knockout (ApoE-/-) mice were fed a 1.25% cholesterol diet for 2, 4, 8, and 12weeks (N=25/group), while a group of ApoE-/- and wild-type Bl-6 mice were fed a normal diet. The study was terminated, and all mice were harvested at 22 weeks of age for vasoreactivity, histology, and protein studies from corporal tissues. Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo. The contents of endothelial cells, smooth muscle cells, and smooth muscle/collagen ratio were assessed by immunohistochemistry staining or Masson staining. Level of cyclic guanosine monophosphate (cGMP) was detected by enzyme immunoassay assay. Levels of phosphorylated endothelial nitric oxide synthase (p-eNOS)/total eNOS, neuronal nitric oxide synthase (nNOS), and cyclic GMP-dependent kinase (cGK-1) protein were assessed by Western analysis. Results. Abnormalities in endothelium-dependent and endothelium-independent vasoreactivities, endothelial content, smooth muscle/collagen ratio, p-eNOS phosphorylation at Ser1177 only, nNOS, cGMP, and cGK-1 changed with the different durations of the high-cholesterol diet. Conclusions. These data demonstrate that this mouse model is suitable for investigating aspects of hypercholesterolemic ED.

AB - Introduction. Hypercholesterolemia is one of the most important risk factors for the development of erectile dysfunction (ED) in men. Aim. We employed an established mouse model of hypercholesterolemia. Main Outcome Measures. We test for abnormalities in vasoreactivity in corporal tissue and temporally correlated changes in vasoreactivity with alterations in histology and protein expression. Methods. A total of 150 mice were studied. A total of 100 apolipoprotein-E knockout (ApoE-/-) mice were fed a 1.25% cholesterol diet for 2, 4, 8, and 12weeks (N=25/group), while a group of ApoE-/- and wild-type Bl-6 mice were fed a normal diet. The study was terminated, and all mice were harvested at 22 weeks of age for vasoreactivity, histology, and protein studies from corporal tissues. Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo. The contents of endothelial cells, smooth muscle cells, and smooth muscle/collagen ratio were assessed by immunohistochemistry staining or Masson staining. Level of cyclic guanosine monophosphate (cGMP) was detected by enzyme immunoassay assay. Levels of phosphorylated endothelial nitric oxide synthase (p-eNOS)/total eNOS, neuronal nitric oxide synthase (nNOS), and cyclic GMP-dependent kinase (cGK-1) protein were assessed by Western analysis. Results. Abnormalities in endothelium-dependent and endothelium-independent vasoreactivities, endothelial content, smooth muscle/collagen ratio, p-eNOS phosphorylation at Ser1177 only, nNOS, cGMP, and cGK-1 changed with the different durations of the high-cholesterol diet. Conclusions. These data demonstrate that this mouse model is suitable for investigating aspects of hypercholesterolemic ED.

KW - Endothelium

KW - Impotence

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KW - Penis

KW - Vascular smooth muscle

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