Thioredoxin reverses age-related hypertension by chronically improving vascular redox and restoring eNOS function.
The incidence of high blood pressure with advancing age is notably high, and it is an independent prognostic factor for the onset or progression of a variety of cardiovascular disorders. Although age-related hypertension is an established phenomenon, current treatments are only palliative but not curative. Thus, there is a critical need for a curative therapy against age-related hypertension, which could greatly decrease the incidence of cardiovascular disorders. We show that overexpression of human thioredoxin (TRX), a redox protein, in mice prevents age-related hypertension. Further, injection of recombinant human TRX (rhTRX) for three consecutive days reversed hypertension in aged wild-type mice, and this effect lasted for at least 20 days. Arteries of wild-type mice injected with rhTRX or mice with TRX overexpression exhibited decreased arterial stiffness, greater endothelium-dependent relaxation, increased nitric oxide production, and decreased superoxide anion (O2•-) generation compared to either saline-injected aged wild-type mice or mice with TRX deficiency. Our study demonstrates a potential translational role of rhTRX in reversing age-related hypertension with long-lasting efficacy.
Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6598, Lubbock, TX 79430, USA.
Rob H P
RH
Hilgers
Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6598, Lubbock, TX 79430, USA.
Venkatesh
V
Kundumani-Sridharan
Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6598, Lubbock, TX 79430, USA.
Jaganathan
J
Subramani
Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6598, Lubbock, TX 79430, USA.
Leon C
LC
Chen
Department of Cell Physiology and Molecular Biophysics, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Luis G
LG
Cuello
Department of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, 4301 Markham Street, Little Rock, AR 72205, USA.
Nancy J
NJ
Rusch
Department of Anesthesiology, Texas Tech University Health Sciences Center, 3601 4th Street, MS 6598, Lubbock, TX 79430, USA. kumuda.das2@uthct.edu.
Kumuda C
KC
Das
D000375:Aging / Q000473:pathology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology* / Q000503:physiopathology; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019255:NADPH Oxidases / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism; D013879:Thioredoxins / Q000494:pharmacology / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D011994:Recombinant Proteins; D013481:Superoxides; D013879:Thioredoxins; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; D005978:Glutathione