Dehydroepiandrosterone, Over-studied but Under-used in the Treatment of Vascular Remodeling Diseases

Roxane Paulin

doi:10.4172/2157-7536.s3-001

Abstract

Vascular remodeling is characterized by a narrowing of the lumen of the vessels, resulting in decreased blood flow, increased pressure and heart failure. This process is found in diseases like atherosclerosis, restenosis after angioplasty, transplants coronary disease, systemic and pulmonary hypertensive vascular disease, and is stimulated by elevated levels of cholesterol, inflammation, oxidative stress, excess of vasodilating molecules and growth factors. Efficient treatments able to fix or prevent the progression of this process are still missing. The hormone dehydroepiandrosterone (DHEA), which levels decrease with aging while cardiovascular risks increase, was hypothesized to have a role in the pathophysiology of vascular diseases. Despite the fact that numerous properties such as fat-reducing, anti-oxidant, vasodilating, anti-inflammatory and anti-proliferative have emerged from two decade of studies, DHEA remain clinically underused in the treatment of vascular remodeling diseases. The lack of understanding of the exact mechanism of action and some controversial epidemiological studies are not foreign to the fact that DHEA is shunned. Nonetheless, we believe that DHEA cannot be ignored since promising results were obtained pre-clinically and clinically in the treatment of vascular remodeling diseases. We are probably close to understand the function of this molecule, especially by its action as a peroxisome proliferator, and it will be a shame to deprive patient of a way to improve their quality of life, or worst a way to extend their survival.

Highlights

Inward inappropriate vascular remodeling is a common feature of several diseases like atherosclerosis, restenosis after angioplasty, transplants coronary disease, systemic and pulmonary hypertensive vascular disease [1] causing a narrowing of the lumen and decreasing maximal flow rates
The first reason that can explain this skepticism is in part due to controversial epidemiologic studies. These studies are often performed by measurement of endogenous DHEAS, and never on DHEA directly, which is understandable considering the fact that DHEAS is the circulatory form of DHEA, more stable and no representative/ correlative to DHEA levels and variations
Close to 30 years after the first studies, no specific toxicity has been described for DHEA, and we are close to define the exact action of DHEA

Summary

Introduction

Inward inappropriate vascular remodeling is a common feature of several diseases like atherosclerosis, restenosis after angioplasty, transplants coronary disease, systemic and pulmonary hypertensive vascular disease [1] causing a narrowing of the lumen and decreasing maximal flow rates. Remodeling occurs in response to various stimuli that disrupt the usually ordered multilayered structure of the wall by activating VSMCs. Elevated cholesterol levels, inflammation, oxidative stress, excess of vasodilating molecules and growth factor are potent stimuli that are found in these diseases. Studies performed on Sardinian males bearing a Mediterranean variant of G6PDH deficiency, support the hypothesis that reduced G6PDH activity has a beneficial affect on age-related disease development. These individuals arbor reduced mortality rates from cerebrovascular and cardiovascular diseases and seems to be more likely to achieve centenarian [11].

Cellular Mechanism of Steroids

DHEA Vasodilating Properties

HYPERPLASY PULMONARY ARTERIAL

Discussion