PTH/PTHrP Receptor Signaling Restricts Arterial Fibrosis in Diabetic LDLR^-/- Mice by Inhibiting Myocardin-Related Transcription Factor Relays.

ABSTRACT:

Rationale

The PTH1R (PTH [parathyroid hormone]/PTHrP [PTH-related protein] receptor) is expressed in vascular smooth muscle (VSM) and increased VSM PTH1R signaling mitigates diet-induced arteriosclerosis in LDLR^-/- mice.

Objective

To study the impact of VSM PTH1R deficiency, we generated mice SM22-Cre:PTH1R(fl/fl);LDLR^-/- mice (PTH1R-VKO) and Cre-negative controls.

Methods and results

Immunofluorescence and Western blot confirmed PTH1R expression in arterial VSM that was reduced by Cre-mediated knockout. PTH1R-VKO cohorts exhibited increased aortic collagen accumulation in vivo, and VSM cultures from PTH1R-VKO mice elaborated more collagen (2.5-fold; P=0.01) with elevated Col3a1 and Col1a1 expression. To better understand the

SUBMITTER: Behrmann A 

PROVIDER: S-EPMC7524585 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature