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Effect of aging and cardiovascular risk factors on receptor Tie1 expression in human erectile tissue
João Fonseca1, Nuno Tomada, Alexandre Magalhães
1Department of Experimental Biology, Faculty of Medicine, Universidade do Porto, Porto, Portugal; Institute for Molecular and Cell Biology (IBMC), Universidade do Porto, Porto, Portugal.
Introduction:
Erectile dysfunction is highly prevalent in patients with advanced age or cardiovascular disease risk factors (CVDRFs). These conditions interfere on expression of vascular growth factors and respective receptors causing disturbance in endothelial function.
Aim:
This study aims to assess the effect of aging and CVDRF on the expression of tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie) 1 in human corpus cavernosum (CC).
Methods:
CC fragments obtained from programmed surgeries or organ donors were divided into three groups: young, healthy aged, and aged with CVDRF. Angiopoietin (Ang) 1, Ang2, Tie1, and Tie2 mRNA and protein levels were assessed by real-time polymerase chain reaction and Western blotting, respectively. Dual-immunolabeling of Tie1 with specific markers of endothelium and smooth muscle and Ang1 and Ang2 was performed.
Main Outcome Measures:
To characterize the expression of Tie1 in human CC and elucidate its potential inhibitory effect in Ang-Tie2 system.
Results:
Analysis of mRNAs demonstrated a decrease in Tie1 expression in CVDRF individuals compared with aged or young healthy individuals. No variation for Tie2, Ang1, or Ang2 expression was observed among the studied groups. In all analyzed CC fragments, a 125 kDa band, Tie1, was detected. This protein presented a significant age-related decrease, specially in individuals with CVDRF. Immunofluorescence study revealed Tie1 expression in the endothelium of samples of all experimental groups.
Conclusions:
Employing different methodological approaches, we show for the first time that Tie1 is expressed in human CC endothelium, and its level of expression diminishes in aged individuals, particularly those with CVDRF. This finding reinforces the view that delivery of Ang1 to the CC of erectile dysfunction affected CVDRF patients is able to activate a beneficial Tie2 response.
Insights
Erectile dysfunction is linked to lower Tie1 (tyrosine kinase with immunoglobulin-like and EGF-like domains 1) levels in aging men, especially those with cardiovascular disease risk factors (CVDRFs). This suggests Tie1 is crucial for penile endothelial function.
Area of Science:
- Urology
- Cardiovascular Research
- Molecular Biology
Background:
- Erectile dysfunction (ED) is common in aging men and those with cardiovascular disease risk factors (CVDRFs).
- These conditions negatively impact endothelial function by altering vascular growth factor expression.
- The role of specific vascular factors like Tie1 in penile tissue is not fully understood.
Purpose of the Study:
- To investigate the expression of tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (Tie1) in the human corpus cavernosum (CC).
- To determine how aging and CVDRFs affect Tie1 expression in the CC.
- To explore Tie1's role within the Angiopoietin-Tie2 signaling pathway in penile tissue.
Main Methods:
- Human CC tissue samples were obtained from young, healthy aged, and aged individuals with CVDRFs.
- Messenger RNA (mRNA) and protein levels of Angiopoietin (Ang) 1, Ang2, Tie1, and Tie2 were quantified using real-time PCR and Western blotting.
- Dual-immunolabeling was performed to localize Tie1, Ang1, and Ang2 within endothelial and smooth muscle cells.
Main Results:
- Tie1 mRNA levels were significantly reduced in individuals with CVDRFs compared to young and healthy aged groups.
- Tie1 protein levels showed a significant age-related decrease, particularly pronounced in individuals with CVDRFs.
- No significant changes in Tie2, Ang1, or Ang2 expression were observed across the groups; Tie1 was localized to the endothelium.
Conclusions:
- Tie1 is expressed in the human corpus cavernosum endothelium, with expression decreasing in aged individuals, especially those with CVDRFs.
- Reduced Tie1 expression in the CC may contribute to endothelial dysfunction associated with aging and CVDRFs.
- Targeting the Angiopoietin-Tie2 system, potentially by enhancing Tie1 function or Ang1 delivery, could be a therapeutic strategy for ED in affected patients.
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