Connecting the dots: Aging, Blood Glucose Control, and Cardiovascular Health
In exploring the literature for connections among aging, blood glucose balance, and cardiovascular disease (CVD), we need to look carefully at DHEA. Firstly, we know that DHEA levels decline with increasing age. Secondly, we know that atherosclerosis is an inflammatory disease (falling under the category of CVD). Thirdly, we know that more diabetics die of heart attacks than of diabetes. We also know that DHEA levels are significantly lower in diabetics than in age-matched non-diabetics. The study below indicates that DHEA-sulfate can impact inflammatory processes that damage blood vessel walls and potentially, inhibit atherosclerotic CVD. Connecting the dots: DHEA may be a critical factor in restoring and protecting cardiovascular health, and thus, in the health and longevity of the diabetic.
Altman R, Motton DD, Kota RS, Rutledge JC. Inhibition of vascular inflammation by dehydroepiandrosterone sulfate in human aortic endothelial cells: roles of PPARalpha and NF-kappaB. Vascul Pharmacol. 2008 Feb-Mar;48(2-3):76-84. Epub 2007 Dec 15.
Division of Endocrinology, Department of Internal Medicine, School of Medicine, University of California, Davis, CA 95616, United States.
Dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal gland and is a precursor for both androgens and estrogens. Atherosclerosis is a well characterized inflammatory disease, but little is known about the role of DHEAS in vascular inflammation. We hypothesize that DHEAS can reduce inflammation in vascular endothelial cells and the mechanism involves the peroxisome proliferator-activated receptor alpha (PPARalpha), thereby inhibiting transcription factors involved in endothelial cell inflammation. To test our hypothesis, aortic endothelial cells were pretreated for 48 h with DHEAS, then with TNF-alpha. TNF-alpha-induced upregulation of the expression of inflammatory genes interleukin (IL)-8 and intracellular adhesion molecule (ICAM)-1 was attenuated by incubation with DHEAS. DHEAS inhibited the TNF-alpha-induced surface expression of vascular cell adhesion molecule (VCAM)-1. This effect was abolished by the addition of MK866, a PPARalpha inhibitor, indicating that PPARalpha is involved in the mechanism of this inhibition. The addition of the aromatase inhibitor letrozole had no effect on the inhibition of TNF-alpha-induced VCAM-1 expression by DHEAS. Treatment of endothelial cells with DHEAS dramatically inhibited the TNF-alpha-induced activation of NF-kappaB, an inflammatory transcription factor, and increased protein levels of the NF-kappaB inhibitor, IkappaB-alpha. These results signify the ability of DHEAS to directly inhibit the inflammatory process and show a potential direct effect of DHEAS on vascular inflammation that has implications for the development of atherosclerotic cardiovascular disease.
