[Estrogens and risks for onset of atherosclerosis]

Area of Science:

• Endocrinology
• Cardiovascular Medicine
• Molecular Biology

Context:

• Premenopausal women exhibit lower coronary heart disease (CHD) risk compared to age-matched men, a protective effect diminished post-menopause.
• Estrogens influence plasma lipoproteins, increasing high-density lipoprotein (HDL) and decreasing low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)].
• Lipid profile changes alone do not fully explain estrogen's cardioprotective effects, suggesting additional mechanisms.

Purpose:

• To explore the multifaceted mechanisms by which estrogens exert cardioprotective effects beyond lipid modification.
• To investigate the role of estrogens in preventing low-density lipoprotein (LDL) oxidation.
• To examine the impact of estrogens on vascular endothelium function, including adhesion molecules and inflammatory mediators.

Summary:

• Estrogens demonstrate cardioprotective properties by favorably altering lipid profiles (increasing HDL, decreasing LDL and Lp(a)) and preventing LDL oxidation.
• Estrogens exert direct vascular effects, reducing adhesion molecule expression (e.g., VCAM-1) and decreasing pro-inflammatory chemokines (e.g., TNF-alpha, IL-1, MCP-1) and growth factors (e.g., PDGF).
• Estrogens also reduce levels of fibrinogen and homocysteine, independent risk factors for CHD.

Impact:

• Recent randomized controlled trials (RCTs) on hormone replacement therapy (HRT) have yielded results inconsistent with previous observational studies suggesting HRT's benefits for CHD.
• The definitive impact of HRT on CHD remains under investigation, pending outcomes from several ongoing clinical trials.
• Understanding these mechanisms is crucial for developing targeted therapies for cardiovascular disease prevention in women.