PTOV1: a novel testosterone-induced atherogenic gene in human aorta

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Molecular Biology

Background:

• Gender differences in atherosclerosis development may involve sex steroid hormones.
• Testosterone's role in atherosclerosis is linked to androgen receptor (AR)-mediated vascular smooth muscle cell (VSMC) proliferation.
• The specific genes involved in testosterone-induced VSMC proliferation are not well understood.

Purpose of the Study:

• To identify genes induced by testosterone that promote VSMC proliferation.
• To investigate the role of identified genes in VSMC proliferation.
• To assess the clinical relevance of these genes in human atherosclerosis.

Main Methods:

• Microarray analysis and quantitative RT-PCR to detect testosterone-induced gene expression in AR-positive human VSMCs.
• Small interfering RNA (siRNA) transfection to inhibit gene function and assess effects on cell proliferation.
• Immunohistochemical evaluation of gene product expression in human aorta samples.

Main Results:

• Testosterone significantly induced the expression of the prostate overexpressed protein 1 (PTOV1) gene in VSMCs.
• Inhibition of PTOV1 using siRNA suppressed testosterone-induced VSMC proliferation.
• PTOV1 was highly expressed in the nuclei of neointimal VSMCs in male aortas with mild atherosclerosis, but less so in female aortas or male aortas with severe disease.

Conclusions:

• The PTOV1 gene is androgen-responsive in VSMCs.
• PTOV1 plays a role in regulating neointimal VSMC proliferation.
• PTOV1 may be a key factor in androgen-related atherogenesis, particularly in early male atherosclerosis.