Flow (shear stress)-mediated remodeling of resistance arteries in diabetes.
ABSTRACT Shear stress due to blood flow is the most important force stimulating vascular endothelium. Acute stimulation of the endothelium by shear stress induces a vasodilatation mainly due to the release of nitric oxide (NO) among other relaxing agents. After a chronic increase in blood flow (shear stress), the endothelium triggers diameter enlargement, medial hypertrophy and improvement of arterial contractility and endothelium-mediated dilation. Shear stress-mediated outward remodeling requires an initial inflammatory response followed by the production of reactive oxygen species (ROS) and peroxinitrite anions, which activate MMPs and extracellular matrix digestion allowing diameter expansion. This outward remodeling occurs in collateral growth following occlusion of a large artery. In diabetes, an excessive ROS production is associated with the formation of advanced glycation end-products (AGEs) and the glycation of enzymes involved in vascular tone. The balance between inflammation, AGEs and ROS level determines the ability of resistance arteries to develop outward remodeling whereas AGEs and ROS contribute to decrease endothelium-mediated dilation in remodeled vessels. This review explores the interaction between ROS, AGEs and the endothelium in shear stress-mediated outward remodeling of resistance arteries in diabetes. Restoring or maintaining this remodeling is essential for an efficient blood flow in distal organs.
- SourceAvailable from: Gilles Kauffenstein[Show abstract] [Hide abstract]
ABSTRACT: Hypertension is a major risk factor for cardiovascular disorders. As flow-mediated outward remodeling has a key role in postischemic revascularization, we investigated this remodeling in mesenteric resistance arteries of normotensive (WKY) and spontaneously hypertensive rats (SHRs) aged 3 to 9 months. Sequential ligation of mesenteric resistance arteries allowed modifying blood flow in vivo, thus exposing arteries to low, normal, or high flow. After 1, 3, 8, or 24 weeks, arteries were isolated for in vitro study. High flow (HF) induced outward hypertrophic remodeling in WKY rats after 1 week and persisted until 24 weeks without change in wall to lumen ratio. In SHRs, diameter increase was delayed, occurring only after 3 weeks. Nevertheless, it was reduced at 8 weeks and no longer significant after 24 weeks. In parallel, media cross-section area increased more with time in SHRs than in WKY rats and this was associated with increased contractility and oxidative stress with decreased NO-dependent relaxation. Low flow induced progressive inward remodeling until 24 weeks in both strains with excessive hypertrophy in SHRs. Thus, a chronic increase in flow induced transitory diameter expansion and long-lasting hypertrophy in SHRs. This could contribute to the higher susceptibility of hypertensive subjects to ischemic diseases.International journal of hypertension. 01/2014; 2014:859793.
- [Show abstract] [Hide abstract]
ABSTRACT: In resistance arteries a chronic increase in blood flow induces hypertrophic outward remodeling. This flow-mediated remodeling (FMR) is absent in male rats aged 10 months and more. As FMR depends on estrogens in 3-month old female rats, we hypothesized that it might be preserved in 12-month old female rats. Blood flow was increased in vivo in mesenteric resistance arteries after ligating side arteries in 3- and 12-month old male and female rats. After 2 weeks, high (HF) and normal flow (NF) arteries were isolated for in vitro analysis. Arterial diameter and cross sectional area increased in HF, compared to NF arteries, in 3-month old male and female rats. In 12-month old rats, diameter increased only in female rats. Endothelial NO-synthase expression and endothelium-mediated relaxation were higher in HF than in NF arteries in all groups. ERK1/2 phosphorylation, NADPHoxidase subunits expression level and arterial contractility to KCl and to phenylephrine were greater in HF than in NF vessels in 12-month old male rats only. Ovariectomy in 12-month old female rats induced a similar pattern with an increased contractility without diameter increase in HF arteries. Treatment of 12-month old male rats and ovariectomized female rats with hydralazine, the antioxidant TEMPOL or the angiotensin II type 1 receptor blocker candesartan restored HF-remodeling and normalized arterial contractility in HF vessels. Thus, we found that FMR of resistance arteries remains efficient in 12-month old female rats compared to age-matched male rats. A balance between estrogens and vascular contractility might preserve FMR in mature female rats.AJP Heart and Circulatory Physiology 06/2014; · 4.01 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed.International Journal of Molecular Sciences 12/2014; 15(12):23792-23835. · 2.46 Impact Factor