Beneficial effects of lifelong caloric restriction on endothelial function are greater in conduit arteries compared to cerebral resistance arteries

OBJECTIVE: Growth hormone (GH) and oestrogen (E(2)) are associated with beneficial effects on the cardiovascular system and it is therefore of great interest to study their interactive effects on haemodynamics and vascular function. DESIGN AND METHODS: Female hypophysectomised (Hx) rats were treated for seven days with GH, E(2) or a combination of the hormones. Systolic blood pressure (SBP), heart rate (HR) and plasma insulin-like growth factor-I (IGF-I) were measured. Contractile properties and endothelial function were studied in isolated resistance arteries using the wire-myograph technique. RESULTS: Hypophysectomy, per se, caused a fall in SBP and HR, while vascular adrenergic reactivity (sensitivity to applied noradrenaline) was enhanced. Impaired acetylcholine-induced relaxation and basal release of nitric oxide, suggests endothelial dysfunction after Hx. After supplementation with GH, SBP remained low while HR increased towards the control level. GH increased plasma IGF-I, but had no effect on vascular contractility or endothelial responses. E(2) replacement resulted in blunted plasma IGF-I, while the vascular adrenergic and serotonergic responses were reinforced. Endothelial function was not improved after E(2) treatment. When GH and E(2) were given in combination, the GH-induced increase in body weight, plasma IGF-I levels and HR were counteracted by E(2). Moreover, the anticipated reinforcement of the vascular serotonergic response by E(2) was reduced. Neither E(2) nor GH+E(2) affected SBP. CONCLUSIONS: The results suggest that GH and E(2) might have interactive effects on haemodynamic and metabolic parameters, but not on the contractility or endothelial function of resistance arteries, in Hx female rats.

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Benidipine Improves Endothelial Function in Renal Resistance Arteries of Hypertensive Rats

Hypertension ◽

10.1161/01.hyp.28.1.58 ◽

1996 ◽

Vol 28 (1) ◽

pp. 58-63 ◽

Cited By ~ 41

Author(s):

Yasuaki Dohi ◽

Masayoshi Kojima ◽

Koichi Sato

Keyword(s):

Endothelial Function ◽

Resistance Arteries ◽

Hypertensive Rats

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Long-Term Caloric Restriction Attenuates β-Amyloid Neuropathology and Is Accompanied by Autophagy in APPswe/PS1delta9 Mice

Nutrients ◽

10.3390/nu13030985 ◽

2021 ◽

Vol 13 (3) ◽

pp. 985

Author(s):

Luisa Müller ◽

Nicole Power Guerra ◽

Jan Stenzel ◽

Claire Rühlmann ◽

Tobias Lindner ◽

...

Keyword(s):

Caloric Restriction ◽

Neuroprotective Effect ◽

Resonance Spectroscopy ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Positron Emission ◽

Pet Ct ◽

Amyloid Aβ ◽

Β Amyloid

Caloric restriction (CR) slows the aging process, extends lifespan, and exerts neuroprotective effects. It is widely accepted that CR attenuates β-amyloid (Aβ) neuropathology in models of Alzheimer’s disease (AD) by so-far unknown mechanisms. One promising process induced by CR is autophagy, which is known to degrade aggregated proteins such as amyloids. In addition, autophagy positively regulates glucose uptake and may improve cerebral hypometabolism—a hallmark of AD—and, consequently, neural activity. To evaluate this hypothesis, APPswe/PS1delta9 (tg) mice and their littermates (wild-type, wt) underwent CR for either 16 or 68 weeks. Whereas short-term CR for 16 weeks revealed no noteworthy changes of AD phenotype in tg mice, long-term CR for 68 weeks showed beneficial effects. Thus, cerebral glucose metabolism and neuronal integrity were markedly increased upon 68 weeks CR in tg mice, indicated by an elevated hippocampal fluorodeoxyglucose [18F] ([18F]FDG) uptake and increased N-acetylaspartate-to-creatine ratio using positron emission tomography/computer tomography (PET/CT) imaging and magnet resonance spectroscopy (MRS). Improved neuronal activity and integrity resulted in a better cognitive performance within the Morris Water Maze. Moreover, CR for 68 weeks caused a significant increase of LC3BII and p62 protein expression, showing enhanced autophagy. Additionally, a significant decrease of Aβ plaques in tg mice in the hippocampus was observed, accompanied by reduced microgliosis as indicated by significantly decreased numbers of iba1-positive cells. In summary, long-term CR revealed an overall neuroprotective effect in tg mice. Further, this study shows, for the first time, that CR-induced autophagy in tg mice accompanies the observed attenuation of Aβ pathology.

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SP284BETA-TRACE PROTEIN CORRELATES WITH ENDOTHELIAL FUNCTION IN PERIPHERAL RESISTANCE ARTERIES IN END STAGE RENAL DISEASE

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfx145.sp284 ◽

2017 ◽

Vol 32 (suppl_3) ◽

pp. iii202-iii202

Author(s):

Samsul Arefin ◽

Amaryllis Van Craenenbroeck ◽

Neja Mudrovcic ◽

Ann-Christin Bragfors-Helin ◽

Peter Stenvinkel ◽

...

Keyword(s):

Renal Disease ◽

Endothelial Function ◽

End Stage Renal Disease ◽

Peripheral Resistance ◽

Resistance Arteries ◽

Stage Renal Disease ◽

End Stage

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Polarized Proteins in Endothelium and Their Contribution to Function

Journal of Vascular Research ◽

10.1159/000512618 ◽

2021 ◽

pp. 1-27

Author(s):

Abigail G. Wolpe ◽

Claire A. Ruddiman ◽

Phillip J. Hall ◽

Brant E. Isakson

Keyword(s):

Endothelial Cells ◽

Endothelial Function ◽

Planar Cell Polarity ◽

Protein Localization ◽

Peripheral Resistance ◽

Specific Protein ◽

Resistance Arteries ◽

Extracellular Stimuli ◽

Small Resistance ◽

Signaling Domains

Protein localization in endothelial cells is tightly regulated to create distinct signaling domains within their tight spatial restrictions including luminal membranes, abluminal membranes, and interendothelial junctions, as well as caveolae and calcium signaling domains. Protein localization in endothelial cells is also determined in part by the vascular bed, with differences between arteries and veins and between large and small arteries. Specific protein polarity and localization is essential for endothelial cells in responding to various extracellular stimuli. In this review, we examine protein localization in the endothelium of resistance arteries, with occasional references to other vessels for contrast, and how that polarization contributes to endothelial function and ultimately whole organism physiology. We highlight the protein localization on the luminal surface, discussing important physiological receptors and the glycocalyx. The protein polarization to the abluminal membrane is especially unique in small resistance arteries with the presence of the myoendothelial junction, a signaling microdomain that regulates vasodilation, feedback to smooth muscle cells, and ultimately total peripheral resistance. We also discuss the interendothelial junction, where tight junctions, adherens junctions, and gap junctions all convene and regulate endothelial function. Finally, we address planar cell polarity, or axial polarity, and how this is regulated by mechanosensory signals like blood flow.

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Abstract 12555: The Dual PPAR-α/γ Agonist Aleglitazar Enhances Arteriogenesis, Angiogenesis and Endothelial Function

Circulation ◽

10.1161/circ.130.suppl_2.12555 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Christian Werner ◽

Stephan H Schirmer ◽

Valerie Pavlickova ◽

Michael Böhm ◽

Ulrich Laufs

Keyword(s):

Endothelial Function ◽

Vascular Function ◽

Daily Injection ◽

Peroxisome Proliferator ◽

Fluorescent Microspheres ◽

Artery Ligation ◽

Peroxisome Proliferator Activated Receptor ◽

Beneficial Effects ◽

And Function

Objective: Peroxisome proliferator-activated receptor (PPAR)-α and -γ agonists modify lipid and glucose metabolism. The aim of the study was to characterize the effects of the dual PPAR-α/γ agonist aleglitazar on endothelial function, neoangiogenesis and arteriogenesis in mice and on human endothelial progenitor cells (EPC). Methods and Results: Male C57Bl/6 wild-type (WT, normal chow) and apolipoprotein E-deficient (apoE-/-) mice on Western-type diet (WTD) were treated with aleglitazar (10 mg/kg i.p.) or vehicle by daily injection. Hindlimb ischemia was induced by right femoral artery ligation (FAL). ApoE-/- mice on WTD treated with aleglitazar before FAL were characterized by an improvement of endothelial-dependent laser Doppler perfusion (right/left foot ratio 0.40±0.03) 1 week after FAL compared to controls (R/L foot ratio 0.24±0.01; p<0.001). Collateral-dependent perfusion measured under conditions of maximal vasodilatation 1 week after FAL using fluorescent microspheres was impaired in apoE-/- on WTD compared to WT mice (R/L leg ratio in WT 78±13 vs. apoE-/- 56±6; p<0.001) and was normalized by aleglitazar treatment. Neoangiogenesis was measured in-vivo by subcutaneously implanting discs covered with cell-impermeable filters. The vascularized area of the discs was quantified after 14 days by perfusion of the animals with space-filling fluorescent microspheres. Aleglitazar increased neoangiogenesis in WT mice by 178±18% compared to vehicle (p<0.05). Endothelium-dependent relaxation of aortic rings was impaired in apoE-/- mice on WTD for 6 weeks (relaxation to 52±5% of max. contraction) compared to WT animals (relaxation to 18±5% of max. contraction) (p<0.001). Aleglitazar treatment improved endothelial function (relaxation to 39±5% of max. contraction; p<0.05). In parallel, number and function of EPC were improved in mice. Studies in human EPC showed that 1) aleglitazar’s effects were mediated by both PPAR-α and -γ signalling and Akt and 2) migration and colony forming units were up-regulated by aleglitazar in cultivated EPC from CAD patients. Conclusion: The study provides evidence for beneficial effects of the dual PPAR-α/γ agonist aleglitazar on vascular function in addition to or mediated by its metabolic actions.

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Pressure-Induced Myogenic Responses in Human Isolated Cerebral Resistance Arteries

Stroke ◽

10.1161/01.str.27.12.2287 ◽

1996 ◽

Vol 27 (12) ◽

pp. 2287-2291 ◽

Cited By ~ 31

Author(s):

Sarah J. Wallis ◽

John Firth ◽

William R. Dunn

Keyword(s):

Resistance Arteries ◽

Myogenic Responses ◽

Cerebral Resistance

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Caveolin-1 and caveolin-3 regulate Ca2+ homeostasis of single smooth muscle cells from rat cerebral resistance arteries

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00669.2006 ◽

2007 ◽

Vol 293 (1) ◽

pp. H204-H214 ◽

Cited By ~ 12

Author(s):

T. Kamishima ◽

T. Burdyga ◽

J. A. Gallagher ◽

J. M. Quayle

Keyword(s):

Smooth Muscle ◽

Smooth Muscle Cells ◽

Removal Rate ◽

Muscle Cells ◽

Amino Acid Residues ◽

Resistance Arteries ◽

Inhibitory Peptide ◽

Caveolin 1 ◽

Domain Peptide ◽

Cerebral Resistance

The role of caveolins, signature proteins of caveolae, in arterial Ca2+ regulation is unknown. We investigated modulation of Ca2+ homeostasis by caveolin-1 and caveolin-3 using smooth muscle cells from rat cerebral resistance arteries. Membrane current and Ca2+ transients were simultaneously measured with voltage-clamped single cells. Membrane depolarization triggered Ca2+ current and increased intracellular Ca2+ concentration ([Ca2+]i). After repolarization, elevated [Ca2+]i returned to the resting level. Ca2+ removal rate was determined from the declining phase of the Ca2+ transient. Application of caveolin-1 antibody or caveolin-1 scaffolding domain peptide, corresponding to amino acid residues 82–101 of caveolin-1, significantly slowed Ca2+ removal rate at a measured [Ca2+]i of 250 nM, with little effect at a measured [Ca2+]i of 600 nM. Application of caveolin-3 antibody or caveolin-3 scaffolding domain peptide, corresponding to amino acid residues 55–74 of caveolin-3, also significantly slowed Ca2+ removal rate at a measured [Ca2+]i of 250 nM, with little effect at a measured [Ca2+]i of 600 nM. Likewise, application of calmodulin inhibitory peptide, autocamtide-2-related inhibitory peptide, and cyclosporine A, inhibitors for calmodulin, Ca2+/calmodulin-dependent protein kinase II, and calcineurin, also significantly inhibited Ca2+ removal rate at a measured [Ca2+]i of 250 nM but not at 600 nM. Application of cyclopiazonic acid, a sarcoplasmic reticulum Ca2+ ATPase inhibitor, also significantly inhibited Ca2+ removal rate at a measured [Ca2+]i of 250 nM but not at 600 nM. Our results suggest that caveolin-1 and caveolin-3 are important in Ca2+ removal of resistance artery smooth muscle cells.

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Effects of Blackcurrant Anthocyanin on Endothelial Function and Peripheral Temperature in Young Smokers

Molecules ◽

10.3390/molecules24234295 ◽

2019 ◽

Vol 24 (23) ◽

pp. 4295 ◽

Cited By ~ 2

Author(s):

Toshiko Tomisawa ◽

Naoki Nanashima ◽

Maiko Kitajima ◽

Kasumi Mikami ◽

Shizuka Takamagi ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Endothelial Function ◽

Skin Temperature ◽

Healthy Male ◽

Double Blind ◽

Beneficial Effects ◽

Flow Mediated Dilatation ◽

Young Smokers ◽

Peripheral Temperature ◽

Level 2

Background: Blackcurrant anthocyanin (BCA) is expected to repair endothelial dysfunction, but it remains unclear whether beneficial effects are present in young healthy persons. This study examines whether supplements containing blackcurrant anthocyanin improve endothelial function and peripheral temperature in young smokers. Methods: Young, healthy male nonsmokers (N group: n = 11; mean age 22 ± 2 years) and smokers (S group: n = 13; mean age 21 ± 1 years) were enrolled. A randomized and double-blind trial was designed to compare the effects of no supplement, a supplement containing 50 mg of blackcurrant anthocyanin (supplement A), and a supplement containing 50 mg of blackcurrant anthocyanin plus vitamin E (supplement B) on flow-mediated dilatation (FMD) and skin temperature. Results: Under no supplement, FMD was unchanged during the 2 h period after smoking in the N group, whereas it was decreased during the 2 h period after smoking in the S group. Under the A supplement, FMD was decreased 1 h after smoking and returned to the baseline level 2 h after smoking in the S group. The skin temperature in the area of the foot dorsum was decreased in the S group after smoking compared with that in the N group, who did not smoke, whereas under A and B supplements, it was higher in the S group compared with that in the N group. Conclusions: BCA could attenuate the smoking-induced acute endothelial dysfunction and improve peripheral temperature in young smokers.

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