Thioredoxin, thioredoxin peptides or derivatives for treatment of age-related hypertension

Abstract

The incidence of high blood pressure is strikingly high with advancing age, and is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders (CVD). There is a critical need for a curative therapy against age-related hypertension. Overexpression of human thioredoxin (Trx) a redox protein in mice prevented age-related hypertension. Chronic injection of recombinant human Trx (rhTrx) for 3-consecutive days reversed hypertension in aged wildtype mice that lasted for at least 20 days. Arteries of wildtype mice so injected or mice with Trx overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxations, increased nitric oxide (NO) production and decreased superoxide anion (O2.−) generation compared to appropriate controls. Collectively, a translational role of rhTrx in reversing age-related hypertension with long lasting efficacy is disclosed. Compositions and methods the treatment of cardiovascular disorders (CVD), primarily hypertension, comprise a therapeutically effective amount of thioredoxin-1 (Trx1 polypeptide, a pharmaceutically active Trx1 peptide fragment, or a functional derivative of Trx1 polypeptide or peptide, in a pharmaceutical carrier to ameliorate one or more symptom of the CVD.

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