Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

Abstract

Aldosterone, secreted by the adrenal zona glomerulosa, enhances sodium retention, thus increasing blood volume and pressure. Excessive production of aldosterone results in high blood pressure and contributes to cardiovascular and renal disease, stroke and visual loss. Hypertension is also associated with obesity, which is correlated with other serious health risks as well. Although weight gain is associated with increased blood pressure, the mechanism by which excess fat deposits increase blood pressure remains unclear. Several studies have suggested that aldosterone levels are elevated with obesity and may represent a link between obesity and hypertension. In addition to hypertension, obese patients typically have dyslipidemia, including elevated serum levels of very low-density lipoprotein (VLDL). VLDL, which functions to transport triglycerides from the liver to peripheral tissues, has been demonstrated to stimulate aldosterone production. Recent studies suggest that the signaling pathways activated by VLDL are similar to those utilized by AngII. Thus, VLDL increases cytosolic calcium levels and stimulates phospholipase D (PLD) activity to result in the induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression. These effects seem to be mediated by the ability of VLDL to increase the phosphorylation (activation) of their regulatory transcription factors, such as the cAMP response element-binding (CREB) protein family of transcription factors. Thus, research into the pathways by which VLDL stimulates aldosterone production may identify novel targets for the development of therapies for the treatment of hypertension, particularly those associated with obesity, and other aldosterone-modulated pathologies.

Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017

“…Regarding mechanistic insight, it has been reported that an excess of very low-density lipoproteins (VLDL) can bind to scavenger receptor B-I (SRB-I), which is a cholesterol docking receptor in the mitochondria to result in more production of aldosterone via acute or sustained stimulation of signaling [30,31]. The link between obesity, hypertension and aldosterone could explain the mechanism for lowered HDL-C and elevated BP with increasing age.…”

Lipid profile and left ventricular geometry pattern in obese children

“…Although the pathophysiological explanation of these results is not straightforward, and we didn't measure aldosterone as well as VLDL levels in our patients, we can't exclude the effects of potential signaling pathways activated by the VLDL which resulted in aldosterone overproduction and development of left ventricular hypertrophy. It is now appreciated that left ventricular hypertrophy (LVH) in hypertensive obese patients is not only mediated via clear-cut increase in blood pressure but also by various neuro-hormonal and metabolic factors that independently exert trophic effects on myocytes and non-myocytes in the heart [31,32]. Experimental and clinical evidence clearly indicates that protracted exposure to inappropriately elevated aldosterone levels induces cardiac inflammation and interstitial fibrosis leading to a maladaptive remodeling in the heart and changes in left ventricular structure and function, regardless of the level of blood pressure.…”

Fat tissue and adrenal function: mechanisms of mutual influence

“…Интересно, что ЛПОНП, не содержащие холестерин, также повышают экспрессию гена, кодирующего StaR-протеин, осуществляющего перенос холестерина на внутреннюю мембрану митохондрий, где начинается процесс ферментативного превращения холестерина в стероиды. Недавнее исследование [73,74] демонстрирует участие PLC/IP3/PKC-сигналов в индукции синтеза альдостерона ЛПОНП.…”