The Mechanisms Underlying VLDL-Induced Aldosterone Production

Abstract

Aldosterone is responsible for sodium retention, thus increased blood volume and pressure. Excessive production of aldosterone results in high blood pressure, as well as renal disease, stroke, and visual loss via its effects on blood pressure. Although weight gain is associated with increased blood pressure, it remains unclear how excess fat deposits increase blood pressure. Indeed, overweight and obesity issues are correlated with serious health risks. In addition to hypertension, obese patients typically have high lipoprotein levels; moreover, some studies have suggested that aldosterone levels are also elevated and represent a link between obesity and hypertension. Very low density lipoprotein (VLDL) functions to transport triglycerides from the liver to peripheral tissues. Previous studies have demonstrated that VLDL can stimulate aldosterone production. By analogy with the signaling pathways activated by Angll, including the finding that VLDL increases cytosolic calcium levels, here we show that both phospholipase C (PLC) and phospholipase D (PLD) are involved in VLDL-induced aldosterone production. The effects of VLDL on steroidogeneses are mediated via an ability of these signaling pathways to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression, the early and late limiting steps in aldosterone biosynthesis, presumably byincreasing the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element binding (CREB) protein family of transcription factors.