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Asian Journal of Biomedical and Pharmaceutical Sciences | Volume 8
May 14-15, 2018 | Montreal, Canada
Global Summit on
Biopharma & Biotherapeutics
H
ypertension is a major risk factor for cardiovascular
diseases, and especially poses health problems for
aging people. However, the pathogenesis of hypertension
and the basic mechanism of blood pressure responses to
aging are incompletely understood. Cytosolic thioredoxin
(Trx-1) is a small (12kDa) antioxidant protein that protects
against oxidative stress. As a reducing agent, it regenerates
proteins and enzymes inactivated by oxidation. Considering
that inactivated oxidized vessel protein accumulation is a
major factor in age-related hypertension, we hypothesized
a potential role of Trx-1 in amelioration of age-related
hypertension by regenerating oxidized vessel proteins.
To investigate this possibility, we recently developed a
transgenic mouse line that is deficient in functional Trx-1
(dnTrx-Tg), and a complementary line that overexpresses
functional Trx-1 (Trx-Tg). We observed that young dnTrx-Tg
mice had significantly higher blood pressures than Trx-Tg
mice. However, aged (>2 years) dnTrx-Tg and wild-type (WT)
mice showed markedly decreased arterial relaxation, while
aged Trx-Tg mice continued to function normally. Functional
NO release, phosphorylation of eNOS, and decreased levels
of superoxide generation were observed in aged Trx-Tg mice
in contrast to aged WT or dnTrx-Tg mice. Further, injection
of recombinant human Trx-1 for three consecutive days
reversed hypertension in aged WT mice, and this effect
lasted for at least 20 days. Our study established that the
preservation of vessel redox state in aged mice is critical in
protection against endothelial dysfunction and maintenance
of normal blood pressure. Further, our study shows that
reversal of hypertension in aging could be achieved by
pharmacological intervention with redox-active drugs, which
is a novel conceptual advance over the current treatment
strategies in hypertension.
e:
hilgers@campbell.eduThioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring
eNOS function
Rob H Hilgers
Campbell University, USA