Journal
BIOMOLECULES
Volume 12, Issue 8, Pages -Publisher
MDPI
DOI: 10.3390/biom12081125
Keywords
HSP70; middle-aged animals; vascular contraction; calcium; ROS
Categories
Funding
- NIDDK Diabetic Complications Consortium [RRID:SCR_ 001415, DK076169, DK115255]
- NHLBI [PO1 HL-134604]
Ask authors/readers for more resources
This study found lower levels of HSP70 in the aortas of middle-aged rats, which may lead to a decline in vascular responses to alpha-1 adrenergic stimulation. Functional HSP70 is necessary for proper calcium handling. Additionally, HSP70 inhibitors may result in increased levels of reactive oxygen species in the aortic rings of middle-aged animals.
Aging impairs the expression of HSP70, an emergent player in vascular biology. However, it is unknown if age-related alterations in HSP70 are linked to a decline in arterial function. In this study, we test the hypothesis that the contributions of HSP70 to vascular contraction are diminished in middle-aged animals. We determined the basal levels of HSP70 in the aorta of young and middle-aged Sprague Dawley male rats using Western blotting. Functional studies were performed in a wire myograph system. Force development in response to phenylephrine was assessed in the presence or absence of extracellular calcium (Ca2+), and in aortic rings treated or non-treated with an HSP70 inhibitor. Fluorescent probes were used to evaluate vascular oxidative stress and nitric oxide levels. We report that middle-aged rats have significantly lower levels of HSP70. Blockade of HSP70 attenuated vascular phasic and tonic contraction in isolated aortas. It appears that a functional HSP70 is required for proper Ca2+ handling as inhibition of this protein led to reduced force-displacement in response to Ca2+ dynamics. Furthermore, middle-aged aortic rings exposed to the HSP70 inhibitor display higher reactive oxygen species levels without changes in nitric oxide. In summary, we show that middle-aged animals have lower levels of HSP70 in aortas, which associates with an age-related decline in vascular responses to alpha-1 adrenergic stimulation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available