Augmented contractility of murine femoral arteries in a streptozotocin diabetes model is related to increased phosphorylation of MYPT1

Abstract

Diabetes mellitus (DM) is a metabolic disorder with high prevalence, and a major risk factor for macro‐ and microvascular abnormalities. This study was undertaken to explore the mechanisms of hypercontractility of murine femoral arteries (FA) obtained from mice with streptozotocin (STZ)‐induced diabetes and its relation to the phosphorylation profile of the myosin phosphatase target subunit 1, MYPT1. The immunoreactivity of MYPT1 toward phospho‐MYPT1‐T696, MYPT1‐T853, or MYPT1‐S695, used as a read out for MYPT1 phosphorylation, has been studied by Western Blotting. Contractile activity of FA from control and STZ mice has been studied by wire myography. At basal conditions (no treatment), the immunoreactivity of MYPT1‐T696/T853 was ~2‐fold higher in the STZ arteries compared with controls. No changes in MYPT1‐T696/853 phosphorylation were observed after stimulation with the Thromboxan‐A2 analog, U46619. Neither basal nor U46619‐stimulated phosphorylation of MYPT1 at S695 was affected by STZ treatment. Mechanical distensibility and basal tone of FA obtained from STZ animals were similar to controls. Maximal force after treatment of FA with the contractile agonists phenylephrine (10 μmol/L) or U46619 (1 μmol/L) was augmented in the arteries of STZ mice by ~2‐ and ~1.5‐fold, respectively. In summary, our study suggests that development of a hypercontractile phenotype in murine FA in STZ diabetes is at least partially related to an increase in phosphorylation of MLCP at MYPT1‐T696/853. Interestingly, the phosphorylation at S695 site was not altered in STZ‐induced diabetes, supporting the view that S695 may serve as a sensor for mechanical activity which is not directly involved in tone regulation.

Morphometric analysis of the inferior vena cava and its clinical correlations using abdomino-pelvic computed tomography: Series from a Jordanian population

“…Different approaches have been used to measure IVC diameters for proper filter placement. For example, a radioopaque ruler fixed behind the patient, calibrated intravascular catheter methods, and subtraction of 20 % from the measured transverse IVC diameter on radiography [13,14]. A recent study also suggested that IVC circular geometry using cross-sectional CT should be considered in the measurement of IVC, since the IVC assumes a circular shape after the placement of the filter [13].…”

Vascular Dysfunction in Diabetes and Obesity: Focus on TRP Channels

“…As well, augmented vascular contractility (Xie et al, 2006;Matsumoto et al, 2014;Lubomirov et al, 2019), increased vascular inflammation (Zhang et al, 2008;Ku and Bae, 2016), and stimulated endothelial cells apoptosis (Sheu et al, 2005, Sheu et al, 2008 can cooperate to cause vascular dysfunction (Figure 1A). There are key processes in obesity which collaborate and lead to impairment of vascular function.…”