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Hyperhomocysteinemia and the Endocrine System: Implications for Atherosclerosis and Thrombosis

Department of Medicine, Section of Endocrinology, Tulane University Medical School (V.F.), New Orleans, Louisiana 70112; and the Department of Pathology, University of Arkansas for Medical Sciences and the John L. McClellan Memorial Veterans Hospital (S.C.G., L.M.F.), Little Rock, Arkansas

I. Introduction

II. Methionine-Homocysteine Metabolism

A. Methionine metabolism

B. Regulation of remethylation and transsulfuration of H(e)

III. Nomenclature and Methodology in the Measurement of Plasma H(e)

A. Methionine load test

IV. Determinants of Plasma Homocysteine

A. Physiological

B. Genetics of hyperhomocysteinemia

C. Nutritional

D. Hormones and H(e) metabolism

V. Homocysteine and Diabetes Mellitus (DM)

A. Hyperhomocysteinemia, renal failure, and diabetic nephropathy

B. Effect of glucose and insulin on H(e) metabolism

VI. Hyperhomocysteinemia and Cholesterol Metabolism

VII. Hyperhomocysteinemia in Premature Vascular Disease

A. Epidemiological and prospective studies

B. Studies in patients with established vascular disease

C. Negative studies

D. Effect of low plasma H(e) on cardiovascular disease

VIII. Possible Mechanisms of Accelerated Vascular Disease in Homocysteinemia

A. Platelet dysfunction

B. Coagulation abnormalities

C. Effects on the endothelium

D. Effects of hyperhomocysteinemia on the arterial wall

E. Coinheritance of factor V Leiden in homocystinuria

IX. Management of Hyperhomocysteinemia

A. Prevention of hyperhomocysteinemia

B. Treatment of hyperhomocysteinemia

X. Conclusion

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