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BETAINE INDUCED RELEASE OF TISSUE FACTOR PATHWAY INHIBITOR AND NITRIC OXIDE: IMPLICATIONS IN THE MANAGEMENT OF CARDIOVASCULAR DISEASE
Author(s) -
Iqbal Omer,
Fareed D,
Cunanan J,
Hoppensteadt D,
Messadek J,
Baltasar F,
Fareed J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a655-a
Subject(s) - betaine , homocysteine , nitric oxide , tissue factor pathway inhibitor , pharmacology , chemistry , biochemistry , endocrinology , medicine , tissue factor , coagulation
Betaine (trimethyglycine), isolated from sugar beet (Beta vulgaris) is a widely distributed natural compound and acts as a substrate in the betaine‐homocysteine methyltransferase process converting homocysteine to methionine. Homocysteine is a recognized risk factor for occlusive vascular disease. Betaine is currently registered as an orphan drug to control homocystinuria (Cystadane®, Orphan Medical Inc.). Although Betaine is also known to produce certain effects on the vascular system, the mechanism of these effects are not known. When repeatedly administered orally to normal human volunteers (n=12) at 6 g/OD for one week, Betaine exhibited hypocoagulant responses as measured by thrombelastographic methods. Blood samples drawn included a baseline, one week post oral administration of Betaine administration. Analysis of the plasma samples did not show any significant anticoagulant effects on the global clotting assays such as the PT, APTT. However, tissue factor pathway inhibitor (TFPI) antigen and functional levels were increased as shown below.Nitric oxide (NO) levels were also measured in all of the samples by using a chromogenic method. Betaine administration resulted in an increase (20‐90%). However, unlike the TFPI after the cessation of Betaine administration NO levels dropped to baseline level. These observations suggest that Betaine may have multiple mechanisms by which it facilitates vascular function. The release of TFPI and generation of NO during Betaine administration may be helpful in restoring vascular function.