Estrogen replacement during hypoalbuminemia may enhance atherosclerotic risk.

Abstract

Estrogen replacement therapy is considered antiatherosclerotic because it reduces LDL cholesterol and fibrinogen and increases HDL cholesterol concentrations. However, exogenous estrogen is also known to increase hepatic triglyceride production. Hyperlipidemia in the nephrotic syndrome is probably due to increased lipoprotein secretion into plasma and decreased clearance of lipoprotein cholesterol and triglycerides. Previously, lipid-lowering effects of ovariectomy in analbuminemic rats were observed, suggesting that in the presence of hypoalbuminemia, estrogen replacement may have adverse effects on the lipid profile. To test this hypothesis, ovariectomized control rats and rats with Adriamycin-induced nephrotic syndrome were treated with estradiol. In ovariectomized controls, estradiol reduced plasma LDL cholesterol, apolipoprotein B, and fibrinogen and increased apolipoprotein A-I and triglycerides. Nephrotic rats were characterized by a marked decrease in plasma colloid osmotic pressure, hyperfibrinogenemia, hyperlipidemia, and stimulated hepatic fatty acid synthesis. The beneficial effects of estradiol on LDL cholesterol, apolipoprotein B, and fibrinogen found in ovariectomized controls were not present in estradiol-treated nephrotic rats. This suggests that in hypoalbuminemia, downregulation of the LDL receptor overrides putative estradiol-induced increases in LDL receptor activity. Moreover, estrogen replacement in the nephrotic syndrome doubled fatty acid synthesis and triglyceride secretion, and markedly exacerbated hypertriglyceridemia, suggesting saturation of triglyceride clearance. Thus, severe hypoalbuminemia in rats induces an atherosclerotic metabolic response that is aggravated by estrogen replacement. These findings suggest that estrogen replacement in hypoalbuminemic subjects could be contra-indicated.

• Authors: J A Joles, C Bijleveld, A van Tol, M J Geelen, H A Koomans
• Journal: Journal of the American Society of Nephrology : JASN (J Am Soc Nephrol) Vol. 8 Issue 12 Pg. 1870-6 (Dec 1997) ISSN: 1046-6673 [Print] United States
• PMID: 9402089 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-I
• Apolipoproteins B
• Cholesterol, LDL
• Fatty Acids
• Receptors, LDL
• Serum Albumin
• Triglycerides
• Estradiol
• Doxorubicin
• Fibrinogen

Topics

• Animals
• Apolipoprotein A-I (blood)
• Apolipoproteins B (blood)
• Arteriosclerosis (etiology)
• Cholesterol, LDL (blood)
• Contraindications
• Down-Regulation
• Doxorubicin (toxicity)
• Estradiol (therapeutic use, toxicity)
• Estrogen Replacement Therapy (adverse effects)
• Fatty Acids (biosynthesis)
• Female
• Fibrinogen (analysis)
• Hypertriglyceridemia (chemically induced, etiology)
• Liver (metabolism)
• Liver Function Tests
• Nephrotic Syndrome (chemically induced, complications)
• Ovariectomy
• Rats
• Rats, Sprague-Dawley
• Receptors, LDL (biosynthesis, genetics)
• Risk
• Serum Albumin (deficiency)
• Triglycerides (metabolism)
• Weight Gain