Serum
sulfatides are critical
glycosphingolipids present in
lipoproteins that work as modulators of
thrombosis and hemostasis. Decreased serum
sulfatide levels are suggested by our previous work to be related to
cardiovascular disease (CVD).
Hypertension, known to be an important risk factor for CVD, may affect serum
sulfatide levels. However, how
hypertension affects serum
sulfatides directly and mechanistically is unknown. To elucidate these possible mechanisms, we investigated changes in serum
sulfatide levels and their metabolism using an established experimental model of
hypertension that uses continuous infusion of
angiotensin II (AngII) into mice. Furthermore, we also examined the effects of four different
antihypertensive drugs (
losartan,
irbesartan,
nifedipine, and
hydralazine) on serum
sulfatide metabolism. Serum levels of
sulfatides were found to be decreased in groups in which only
hypertension was induced (AngII only), whereas they were increased in groups with reduced blood pressure (
antihypertensives only) and ameliorated to increasingly normal levels in groups with induced
hypertension that were also treated (AngII+antihypertensives). Changes in serum
sulfatides were strongly related to hepatic expression levels of
cerebroside sulfotransferase (CST), which is a key
enzyme involved in
sulfatide synthesis. Furthermore, the current study suggests that the primary factors affecting CST expression are oxidative stress,
peroxisome proliferator-activated receptor α activity and blood pressure itself. This study demonstrates that
hypertension significantly decreases levels of serum
sulfatides by reducing hepatic CST expression via various effects mediated by AngII.
Antihypertensive treatments can ameliorate abnormalities in serum
sulfatide levels and may partially prevent
hypertension related CVD by positively affecting
sulfatide metabolism.