Article

Flow (shear stress)-mediated remodeling of resistance arteries in diabetes

Dept of Integrated Neurovascular and Mitochondrial Biology, UMR CNRS 6214-INSERM 1083, University of Angers, France
Vascular Pharmacology (Impact Factor: 4.62). 03/2012; 57(5-6):173-8. DOI: 10.1016/j.vph.2012.03.006
Source: PubMed

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.

0 Followers
 · 
105 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Objective: Endocan, a dermatan sulphate proteoglycan produced by endothelial cells, is considered a biomarker for endothelial cell activation/dysfunction. Preeclampsia (PE) is characterized by systemic vascular inflammation, and endothelial cell activation/ dysfunction. Therefore, the objectives of this study were to determine if: 1) plasma endocan concentrations in PE differ from that of uncomplicated pregnancy; 2) changes in plasma endocan concentration relate to the severity of preeclampsia, and whether these changes are specific or observed in other obstetrical syndromes such as small-for-gestational age (SGA), fetal death (FD), preterm labor (PTL) or preterm prelabor rupture of membranes (PROM); 3) a correlation exists between plasma concentration of endocan and angiogenic (placental growth factor or PlGF) /anti-angiogenic factors (soluble vascular endothelial growth factor receptor or sVEGFR-1, and soluble endoglin or sEng) among pregnancies complicated by PE; and 4) plasma endocan concentrations in patients with preeclampsia and acute pyelonephritis (both conditions in which there is endothelial cell activation) differ. Method: This cross-sectional study included the following groups: 1) uncomplicated pregnancy (n=130); 2) preeclampsia (n=102); 3) pregnant women without preeclampsia who delivered a SGA neonate (n= 51); 4) FD (n=49); 5) acute pyelonephritis (AP; n=35); 6) spontaneous PTL (n=75); and 7) preterm PROM (n= 64). Plasma endocan concentrations were determined in all groups, and PIGF, sEng and VEGFR-1 plasma concentrations were measured by ELISA in the preeclampsia group. Results: 1) Women with preeclampsia had a significantly higher median plasma endocan concentration than those with uncomplicated pregnancies (p= 0.004); 2) among women with preeclampsia, the median plasma endocan concentration did not differ significantly according to disease severity (p=0.1), abnormal uterine artery Doppler velocimetry (p =0.7), or whether diagnosis was made before or after 34 weeks gestational age (p=0.3); 3) plasma endocan concentration in women with preeclampsia correlated positively with plasma anti-angiogenic factor concentrations [ sVEGFR-1:Spearman rho 0.34, p=0.001 and sEng: Spearman rho 0.30, p=0.003]; 4) pregnancies complicated by acute pyelonephritis with bacteremia had a lower median plasma endocan concentration than pregnancies complicated by acute pyelonephritis without bacteremia (p=0.004), as well as uncomplicated pregnancies (p=0.001); and 5) there was no significant difference in the median plasma endocan concentration between uncomplicated pregnancies and those complicated by FD, delivery of an SGA neonate, PTL or preterm PROM (other members of the "great obstetrical syndromes"; each p>0.05). Conclusion: The median maternal plasma endocan concentrations were higher preeclampsia and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in the direction of change of endocan in preeclampsia and acute pyelonephritis with bacteremia may be consistent with the view that both disease entities differ in pathogenic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction.
    Journal of Maternal-Fetal and Neonatal Medicine 09/2014; DOI:10.3109/14767058.2014.964676 · 1.21 Impact Factor
  • Source
    [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. DOI:10.3390/ijms151223792 · 2.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Ischemia impairs blood supply to the brain and reperfusion is important to restore cerebral blood flow (CBF) and rescue neurons from cell death. However, reperfusion can induce CBF values exceeding the basal values prior to ischemia. This hyperemic effect has been associated with a worse ischemic brain damage, albeit the mechanisms that contribute to infarct expansion are not clear. In this study, we investigated the influence of early postischemic hyperemia on brain damage and middle cerebral artery (MCA) properties, and the effect of treatment with the endogenous antioxidant uric acid (UA). The MCA was occluded for 90 min followed by 24 h reperfusion in adult male Sprague-Dawley rats. Cortical CBF increases at reperfusion beyond 20% of basal values were taken as indicative of hyperemia. UA (16 mg/kg) or vehicle (Locke's buffer) was administered i.v. 135 min after MCA occlusion. Hyperemic compared to non-hyperemic rats showed MCA wall thickening (sham: 22.4 ± 0.8 μm; non-hyperemic: 23.1 ± 1.2 μm; hyperemic: 27.8 ± 0.9 at 60 mmHg; P < 0.001, hyperemic vs. sham) involving adventitial cell proliferation, increased oxidative stress and interleukin-18, and more severe brain damage. Thus, MCA remodeling after ischemia/reperfusion takes place under vascular oxidative and inflammatory stress conditions linked to hyperemia. UA administration attenuated MCA wall thickening, induced passive lumen expansion, and reduced brain damage in hyperemic rats, though it did not increase brain UA concentration. We conclude that hyperemia at reperfusion following brain ischemia induces vascular damage that can be attenuated by administration of the endogenous antioxidant UA. Copyright © 2015, American Journal of Physiology - Heart and Circulatory Physiology.
    AJP Heart and Circulatory Physiology 01/2015; 308(8):ajpheart.00001.2015. DOI:10.1152/ajpheart.00001.2015 · 4.01 Impact Factor