EMAIL THIS PAGE TO A FRIEND

Atherosclerosis

Lack of vitamin D receptor causes stress-induced premature senescence in vascular smooth muscle cells through enhanced local angiotensin-II signals.


PMID 24880896

Abstract

The inhibition of the renal renin-angiotensin system by the active form of vitamin D contributes to the cardiovascular health benefits of a normal vitamin D status. Local production of angiotensin-II in the vascular wall is a potent mediator of oxidative stress, prompting premature senescence. Herein, our objective was to examine the impact of defective vitamin D signalling on local angiotensin-II levels and arterial health. Primary cultures of aortic vascular smooth muscle cells (VSMC) from wild-type and vitamin D receptor-knockout (VDRKO) mice were used for the assessment of cell growth, angiotensin-II and superoxide anion production and expression levels of cathepsin D, angiotensin-II type 1 receptor and p57(Kip2). The inxa0vitro findings were confirmed histologically in aortas from wild-type and VDRKO mice. VSMC from VDRKO mice produced more angiotensin-II in culture, and elicited higher levels of cathepsin D, an enzyme with renin-like activity, and angiotensin-II type 1 receptor, than wild-type mice. Accordingly, VDRKO VSMC showed higher intracellular superoxide anion production, which could be suppressed by cathepsin D, angiotensin-II type 1 receptor or NADPH oxidase antagonists. VDRKO cells presented higher levels of p57(Kip2), impaired proliferation and premature senescence, all of them blunted upon inhibition of angiotensin-II signalling. Inxa0vivo studies confirmed higher levels of cathepsin D, angiotensin-II type 1 receptor and p57(Kip2) in aortas from VDRKO mice. The beneficial effects of active vitamin D in vascular health could be a result of the attenuation of local production of angiotensin-II and downstream free radicals, thus preventing the premature senescence of VSMC.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

HPA003596
Anti-AGTR1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2100073
Anti-AGTR1 antibody produced in rabbit, affinity isolated antibody
SAB3500209
Anti-AGTR1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
GW21178 Anti-ATM antibody produced in chicken, affinity isolated antibody, buffered aqueous solution
SAB3500147
Anti-ATM antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4501968
Anti-ATM antibody produced in rabbit, affinity isolated antibody
A6218 Anti-ATM antibody, Mouse monoclonal, clone SYML6A10, purified from hybridoma cell culture
A6093 Anti-ATM antibody, Mouse monoclonal, clone SYR6D4, purified from hybridoma cell culture
SAB1405677
Anti-CTSD antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA003001
Anti-CTSD antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2106553
Anti-CTSD antibody produced in rabbit, affinity isolated antibody
SAB1410265
Anti-CTSD antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB1406792
Anti-SLC33A1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB2102202
Anti-SLC33A1 antibody produced in rabbit, affinity isolated antibody
HPA042430
Anti-SLC33A1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB1411622
Anti-SLC33A1 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
PLA0045
Goat anti-ATM Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.
SAB1402696
Monoclonal Anti-ATM antibody produced in mouse, clone 2C10, purified immunoglobulin, buffered aqueous solution
A1106
Monoclonal Anti-ATM antibody produced in mouse, ~2 mg/mL, clone MAT3-4G10/8, purified immunoglobulin, PBS solution
C0715
Monoclonal Anti-Cathepsin D antibody produced in mouse, clone CTD-19, ascites fluid
WH0001509M1
Monoclonal Anti-CTSD antibody produced in mouse, clone 3F12-1B9, purified immunoglobulin, buffered aqueous solution
WH0009197M7
Monoclonal Anti-SLC33A1 antibody produced in mouse, clone 3A4, purified immunoglobulin, buffered aqueous solution
PLA0086
Rabbit anti-ATM Antibody, Affinity Purified, Powered by Bethyl Laboratories, Inc.