Description:
<jats:p>
<jats:bold>Objectives:</jats:bold>
Choline enthanolamine phosphotransferase 1 (
<jats:italic>CEPT1</jats:italic>
), is essential for endothelial
<jats:italic>de novo</jats:italic>
lipogenesis (DNL) and is elevated in diseased peripheral arterial segments. Women are more sensitive to diet-induced DNL, and those with diabetes have higher incidence of severe peripheral arterial disease (PAD). We therefore hypothesized that women may have higher
<jats:italic>CEPT1</jats:italic>
content in diseased peripheral arteries and that murine conditional endothelial overexpression of
<jats:italic>CEPT1</jats:italic>
may lead to sex-specific differences in ischemic recovery.
</jats:p>
<jats:p>
<jats:bold>Methods:</jats:bold>
<jats:italic>CEPT1</jats:italic>
expression was evaluated in diseased peripheral plaque of 7 women and 9 men. A murine endothelial
<jats:italic>CEPT1</jats:italic>
overexpression model was engineered with Cre-induced expression of a
<jats:italic>CEPT1</jats:italic>
transgene inserted in a C57BL/6J background. Endothelial
<jats:italic>CEPT1</jats:italic>
overexpression was evaluated using RT-PCR. Male (n=5) and female (n=5) received Streptozotocin and unilateral femoral artery ligation. Limb perfusion, appearance, and use were then evaluated. Gastrocnemius was stained with H&E, and endothelial Isolectin. Muscle fiber size and microvascular density were analyzed using Student’s t-test.
</jats:p>
<jats:p>
<jats:bold>Results:</jats:bold>
Compared to males, female patients have higher
<jats:italic>CEPT1</jats:italic>
in peripheral segments (n=7, p<0.005; Fig A). Murine endothelial
<jats:italic>CEPT1</jats:italic>
overexpression had a 7-fold increase in expression compared to control (Fig B). Compared to female mice, males demonstrated improved perfusion (p<0.05; Fig C,D), limb function (p<0.05; Fig E), limb appearance (p<0.05; Fig E), muscle fiber size (p<0.05; Fig F,G), but both has adequate muscle microvascular density (Fig F,H).
</jats:p>
<jats:p>
<jats:bold>Conclusion:</jats:bold>
This study reveals a gender difference in peripheral arterial
<jats:italic>CEPT1</jats:italic>
expression and ischemic recovery following overexpression. Differences do not appear to be directly associated with angiogenesis and may be due to underlying DNL metabolic consequences. These findings may have important implications for the prevalence of severe PAD in diabetic women.
</jats:p>
<jats:p>
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</jats:p>