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Article ; Online: Effects of low-dose rapamycin on lymphoid organs of mice prone and resistant to accelerated senescence.

Barros, Rafael Dos Santos / Queiroz, Luiz Adriano Damasceno / de Assis, Josiane Betim / Pantoja, Kamilla Costa / Bustia, Sofia Xavier / de Sousa, Emanuella Sarmento Alho / Rodrigues, Stephen Fernandes / Akamine, Eliana Hiromi / Sá-Nunes, Anderson / Martins, Joilson O

Frontiers in immunology

2024 Volume 15, Page(s) 1310505

Abstract: Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to immunosenescence. Here, we ... ...

Abstract	Aging is a complex, natural, and irreversible phenomenon that subjects the body to numerous changes in the physiological process, characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to immunosenescence. Here, we evaluated the regulation of immunosenescence in lymphoid organs of senescence-accelerated prone 8 (SAM-P8) and senescence-accelerated resistant 1 (SAM-R1) mice treated with a low dose of rapamycin (RAPA). Mice were treated with a dose of 7.1 µg/kg RAPA for 2 months and had body mass and hematological parameters analyzed prior and during treatment. Cellular and humoral parameters of serum, bone marrow, thymus, and spleen samples were evaluated by ELISA, histology, and flow cytometry. Changes in body mass, hematological parameters, cell number, and in the secretion of IL-1β, IL-6, TNF-α, IL-7, and IL-15 cytokines were different between the 2 models used. In histological analyses, we observed that SAM-P8 mice showed faster thymic involution than SAM-R1 mice. Regarding the T lymphocyte subpopulations in the spleen, CD4
MeSH term(s)	Mice ; Humans ; Animals ; Sirolimus/pharmacology ; Aging ; T-Lymphocyte Subsets ; CD8-Positive T-Lymphocytes ; Cytokines
Chemical Substances	Sirolimus (W36ZG6FT64) ; Cytokines
Language	English
Publishing date	2024-03-07
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2024.1310505
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Article: Combined Neuroprotective Strategies Blocked Neurodegeneration and Improved Brain Function in Senescence-Accelerated Mice.

Malerba, Helena Nascimento / Pereira, Arthur Antonio Ruiz / Pierrobon, Marcela Favoretto / Abrao, Guilherme Souza / Toricelli, Mariana / Akamine, Eliana Hiromi / Buck, Hudson Sousa / Viel, Tania Araujo

Frontiers in aging neuroscience

2021 Volume 13, Page(s) 681498

Abstract: Increase in the quality of life, combined with drug strategies, has been studied as possibilities for improving memory and delaying the onset of neurodegenerative diseases. A previous study published by the group of the authors has shown that microdose ... ...

Abstract	Increase in the quality of life, combined with drug strategies, has been studied as possibilities for improving memory and delaying the onset of neurodegenerative diseases. A previous study published by the group of the authors has shown that microdose lithium and enriched environment can improve memory in both mice and humans. To elucidate this relationship better, this study aimed to evaluate whether the chronic combination of these two strategies could increase healthy aging in Senescence Accelerated Mouse-Prone 8 (SAMP8). Animals were submitted to either one or both of these strategies until the age of 10 months when they were anesthetized and killed and their hippocampus was extracted. The untreated SAMP-8 group exhibited worse memory and reduced neuronal density with greater neurodegeneration and increased amyloid-β plaque density compared with the control group. Moreover, significant alterations in proteins related to long-term potentiation, such as, synaptophysin and brain-derived neurotrophic factor (BDNF), were observed in this group. The strategies used in the study maintained long-term memory, reduced anxiety, and increased neuroprotection. Both strategies were efficient in reducing neurodegeneration and increasing parameters related to memory maintenance. In many experiments, the combination of the two strategies was more effective in improving healthy aging. This study sheds light on the combination of strategies that choose to improve the quality of life and drugs with low side effects. Moreover, it opens perspectives for a new field of study for healthy aging.
Language	English
Publishing date	2021-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2558898-9
ISSN	1663-4365
ISSN	1663-4365
DOI	10.3389/fnagi.2021.681498
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Article ; Online: Late Onset of Estrogen Therapy Impairs Carotid Function of Senescent Females in Association with Altered Prostanoid Balance and Upregulation of the Variant ERα36.

Costa, Tiago Januário / Jiménez-Altayó, Francesc / Echem, Cinthya / Akamine, Eliana Hiromi / Tostes, Rita / Vila, Elisabet / Dantas, Ana Paula / Carvalho, Maria Helena Catelli de

Cells

2019 Volume 8, Issue 10

Abstract: Recent analysis of clinical trials on estrogen therapy proposes the existence of a therapeutic window of opportunity for the cardiovascular benefits of estrogens, which depend on women's age and the onset of therapy initiation. In this study, we aimed to ...

Abstract	Recent analysis of clinical trials on estrogen therapy proposes the existence of a therapeutic window of opportunity for the cardiovascular benefits of estrogens, which depend on women's age and the onset of therapy initiation. In this study, we aimed to determine how vascular senescence and the onset of estrogen treatment influence the common carotid artery (CCA) function in senescent and non-senescent females. Ovariectomized female senescence-accelerated (SAMP8) or non-senescent (SAMR1) mice were treated with vehicle (OVX) or 17β-estradiol starting at the day of ovariectomy (early-onset, E
MeSH term(s)	Aging ; Animals ; Carotid Arteries/metabolism ; Carotid Arteries/physiopathology ; Estrogen Receptor alpha/genetics ; Estrogens/adverse effects ; Estrogens/therapeutic use ; Female ; Gene Expression Regulation ; Mice ; Prostaglandins/metabolism ; Vasoconstriction
Chemical Substances	Estrogen Receptor alpha ; Estrogens ; Prostaglandins
Language	English
Publishing date	2019-10-08
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells8101217
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Article ; Online: Detrimental Impact of Low Birth Weight on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Healthy Children: Role of Angiogenic Factors.

Souza, Livia Victorino / De Meneck, Franciele / Oliveira, Vanessa / Higa, Elisa Mieko / Akamine, Eliana Hiromi / Franco, Maria do Carmo

The Journal of pediatrics

2019 Volume 206, Page(s) 72–77.e1

Abstract: Objective: To provide a comprehensive assessment of the relationship of birth weight with both endothelial progenitor cell function and angiogenic factors in children.: Study design: Anthropometric measures, biochemical profile, endothelial ... ...

Abstract	Objective: To provide a comprehensive assessment of the relationship of birth weight with both endothelial progenitor cell function and angiogenic factors in children. Study design: Anthropometric measures, biochemical profile, endothelial progenitor cell number, endothelial progenitor cell colony-forming units, vascular endothelial growth factor-A, and nitric oxide plasma levels of 58 children aged 7-11 years were determined. Results: A positive correlation was observed between birth weight and circulating endothelial progenitor cell number (r= 0.461; P= .001), endothelial progenitor cell colony-forming units (r= 0.512; P < .001), vascular endothelial growth factor-A (r= 0.407; P= .002), and nitric oxide (r= 0.547; P < .001) levels, whereas the adjustment for prematurity, family history of cardiovascular disease, and systolic blood pressure levels did not modify these associations. Conclusion: Low birth weight was associated with a decrease in the circulating/functional capacity of endothelial progenitor cells among healthy children, independent of traditional cardiovascular risk factors. This detrimental impact was accompanied by lower circulating levels of angiogenic factors.
MeSH term(s)	Anthropometry ; Birth Weight ; Blood Pressure ; Body Weight ; Cardiovascular Diseases/blood ; Child ; Endothelial Progenitor Cells/cytology ; Female ; Healthy Volunteers ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Leukocytes, Mononuclear/cytology ; Male ; Neovascularization, Physiologic ; Nitric Oxide/blood ; Risk Factors ; Stem Cells/cytology ; Surveys and Questionnaires ; Systole ; Vascular Endothelial Growth Factor A/blood
Chemical Substances	VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2019-02-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2018.10.040
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Article ; Online: Immune spleen cells attenuate the inflammatory profile of the mesenteric perivascular adipose tissue in obese mice.

da Silva, Renée de Nazaré Oliveira / Santos-Eichler, Rosangela Aparecida / Dias, Carolina / Rodrigues, Stephen Fernandes / Skiba, Dominik S / Landgraf, Richardt Gama / de Carvalho, Maria Helena Catelli / Guzik, Tomasz / Fock, Ricardo Ambrósio / Akamine, Eliana Hiromi

Scientific reports

2021 Volume 11, Issue 1, Page(s) 11153

Abstract: The perivascular adipose tissue (PVAT) differs from other fat depots and exerts a paracrine action on the vasculature. The spleen has an important role in the immune response, and it was observed to have either a protective role or a contribution to ... ...

Abstract	The perivascular adipose tissue (PVAT) differs from other fat depots and exerts a paracrine action on the vasculature. The spleen has an important role in the immune response, and it was observed to have either a protective role or a contribution to obesity-related diseases. However, the relation between spleen and PVAT is elusive in obesity. We investigated the role of spleen in the inflammatory profile of the mesenteric PVAT (mPVAT) from mice fed a high-fat diet (HFD) for 16 weeks. Male C57Bl/6 mice were sham-operated or splenectomized (SPX) and fed a HFD for 16 weeks. mPVAT morphology was evaluated by hematoxylin and eosin staining, infiltrated immune cells were evaluated by flow cytometry, inflammatory cytokines were evaluated by ELISA and the splenic cell chemotaxis mediated by mPVAT was evaluated using a transwell assay. In SPX mice, HFD induced adipocyte hypertrophy and increased immune cell infiltration and proinflammatory cytokine levels in mPVAT. However, none of these effects were observed in mPVAT from sham-operated mice. Spleen from HFD fed mice presented reduced total leukocytes and increased inflammatory markers when compared to the spleen from control mice. Chemotaxis of spleen cells mediated by mPVAT of HFD fed mice was reduced in relation to standard diet fed mice. The spleen protects mPVAT against the effects of 16-week HFD. This information was missing, and it is important because PVAT is different from other fat depots and data cannot be extrapolated from any type of adipose tissue to PVAT.
MeSH term(s)	Animals ; Chemotaxis/physiology ; Cytokines/blood ; Diet, High-Fat ; Inflammation/metabolism ; Intra-Abdominal Fat/metabolism ; Male ; Mice ; Obesity/metabolism ; Spleen/metabolism ; Splenectomy
Chemical Substances	Cytokines
Language	English
Publishing date	2021-05-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-90600-0
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Article ; Online: Beneficial Impact of Moderate to Vigorous Physical Activity Program on Circulating Number and Functional Capacity of Endothelial Progenitor Cells in Children: The Crucial Role of Nitric Oxide and VEGF-A.

Souza, Livia Victorino / De Meneck, Franciele / Oliveira, Vanessa / Higa, Elisa Mieko / Akamine, Eliana Hiromi / Franco, Maria do Carmo

Pediatric exercise science

2018 Volume 31, Issue 3, Page(s) 322–329

Abstract: Purpose: Endothelial progenitor cells (EPCs) appear to interact with physical training. This study aimed to provide a comprehensive assessment of the relationship of moderate to vigorous physical activity (MVPA) with both angiogenic factors and EPC ... ...

Abstract	Purpose: Endothelial progenitor cells (EPCs) appear to interact with physical training. This study aimed to provide a comprehensive assessment of the relationship of moderate to vigorous physical activity (MVPA) with both angiogenic factors and EPC function in healthy children. Methods: Forty children (22 boys and 18 girls) aged 7 to 11 years participated in a 10-week MVPA program (duration: 45 min; intensity: 75%-85% of heart rate reserve; frequency: 4 sessions/wk). The anthropometric data, biochemical profile, EPCs number, EPCs colony-forming units, and vascular endothelial growth factor-A (VEGF-A) and nitric oxide (NO) plasma levels were evaluated before and after the MVPA program. Results: After a 10-week MVPA program, a significant increase was detected in circulating/functional capacity of EPCs, NO, and VEGF-A levels, associated with improvement of waist circumference and estimated maximum rate of oxygen consumption (VO2max). A strong positive correlation was found between delta of EPCs number and variation of both NO level (r = .677, P < .001) and VEGF-A level (r = .588, P < .001). Furthermore, a significant correlation between NO level variation and delta of VEGF-A level was observed (r = .708, P < .001). Conclusion: Our findings suggest that lifestyle intervention implemented by MVPA program can contribute meaningfully to improve circulating/functional capacity of EPCs in healthy children, possibly due to the increase of plasma NO and VEGF-A levels.
MeSH term(s)	Cardiorespiratory Fitness ; Child ; Endothelial Progenitor Cells/cytology ; Exercise ; Female ; Humans ; Male ; Nitric Oxide/blood ; Oxygen Consumption ; Vascular Endothelial Growth Factor A/blood ; Waist Circumference
Chemical Substances	VEGFA protein, human ; Vascular Endothelial Growth Factor A ; Nitric Oxide (31C4KY9ESH)
Language	English
Publishing date	2018-10-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1042382-5
ISSN	1543-2920 ; 0899-8493
ISSN (online)	1543-2920
ISSN	0899-8493
DOI	10.1123/pes.2018-0178
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Article ; Online: Systemic arterial hypertension leads to decreased semen quality and alterations in the testicular microcirculation in rats.

Colli, Lucas Giglio / Belardin, Larissa Berloffa / Echem, Cinthya / Akamine, Eliana Hiromi / Antoniassi, Mariana Pereira / Andretta, Rhayza Roberta / Mathias, Lucas Solla / Rodrigues, Stephen Fernandes de Paula / Bertolla, Ricardo Pimenta / de Carvalho, Maria Helena Catelli

Scientific reports

2019 Volume 9, Issue 1, Page(s) 11047

Abstract: Arterial hypertension is a cardiovascular disease that leads to important systemic alterations and drastically impairs normal organ function over time. Hypertension affects around 700 million men of reproductive age and hypertensive men present increased ...

Abstract	Arterial hypertension is a cardiovascular disease that leads to important systemic alterations and drastically impairs normal organ function over time. Hypertension affects around 700 million men of reproductive age and hypertensive men present increased risk for reproductive disorders, such as erectile dysfunction. However, the link between arterial hypertension and male reproductive disorders is associative at best. Moreover, many studies have reported associations between decreased male fertility and/or semen quality and alterations to general male health. In this study we aim to investigate the effect of systemic high blood pressure in sperm quality, sperm functional characteristics and testicular physiology in a rat model. Hypertensive rats presented altered testicular morphology - mainly vascular alterations and impaired testicular vasomotion. Hypertensive rats also presented decrease in sperm concentration, DNA integrity and increased percentages of sperm with dysfunctional mitochondria, intracellular superoxide anion activity and abnormal morphology. This study provides mechanistic insights by which arterial hypertension affects the testes, evidencing the testes as another target organ for hypertension as well as its impact on sperm quality.
MeSH term(s)	Animals ; Cell Shape/physiology ; Hypertension/metabolism ; Hypertension/physiopathology ; Male ; Microcirculation/physiology ; Mitochondria/metabolism ; Rats ; Rats, Inbred SHR ; Rats, Wistar ; Semen/metabolism ; Semen Analysis ; Sperm Motility/physiology ; Spermatozoa/metabolism ; Spermatozoa/pathology ; Superoxides/metabolism ; Testis/blood supply
Chemical Substances	Superoxides (11062-77-4)
Language	English
Publishing date	2019-07-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47157-w
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Article ; Online: Involvement of inducible nitric oxide synthase and estrogen receptor ESR2 (ERβ) in the vascular dysfunction in female type 1 diabetic rats.

Sartoretto, Simone Marcieli / Santos, Fernanda Fernandes / Costa, Beatriz Pereira / Ceravolo, Graziela Scalianti / Santos-Eichler, Rosângela / Carvalho, Maria Helena Catelli / Fortes, Zuleica Bruno / Akamine, Eliana Hiromi

Life sciences

2018 Volume 216, Page(s) 279–286

Abstract: Aims: Inflammation is involved in diabetes-related vascular dysfunction. Estrogen receptor ESR2/ERβ induces the expression of inducible nitric oxide (NO) synthase (iNOS) and inflammation. The present study investigated the effect of alloxan-induced type ...

Abstract	Aims: Inflammation is involved in diabetes-related vascular dysfunction. Estrogen receptor ESR2/ERβ induces the expression of inducible nitric oxide (NO) synthase (iNOS) and inflammation. The present study investigated the effect of alloxan-induced type 1 diabetes on the iNOS and ESR2 expression and the effect of the chronic iNOS inhibition on the vascular smooth muscle dysfunction in diabetic female rats. In addition, we evaluated the involvement of ESR2 in iNOS expression. Main methods: Alloxan-induced diabetic female rats were treated or not with iNOS inhibitor (L-NIL). iNOS and ESR2 immunostaining, S-nitrosylated proteins and IL-1β protein expression in aorta and plasmatic NO levels were analyzed. Contractile response to noradrenaline was analyzed in endothelium-denuded aorta. iNOS mRNA expression was analyzed in isolated aortic smooth muscle cells (ASMCs) of female rats, incubated with 22 mM glucose and an ESR2 antagonist. Key findings: Aortic iNOS and ESR2 immunostaining, S-nitrosylated proteins, IL-1β protein expression and plasmatic NO levels were all increased, whereas noradrenaline-induced contraction was reduced in aorta of diabetic female rats. With the exception of iNOS and ESR2 immunostaining, all these parameters were corrected by L-NIL treatment. High glucose increased iNOS mRNA expression in ASMCs, which was reduced by an ESR2 antagonist. Significance: We demonstrated that increased iNOS-NO contributed to the impairment of the contractile response of aortic smooth muscle cells in female type 1 diabetic rats and that increased expression of iNOS may involve the participation of ESR2/ERβ.
MeSH term(s)	Alloxan ; Animals ; Aorta/pathology ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/physiopathology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/physiopathology ; Endothelium, Vascular/pathology ; Estrogen Receptor beta/genetics ; Female ; Inflammation/genetics ; Inflammation/pathology ; Interleukin-1beta/genetics ; Muscle, Smooth, Vascular/pathology ; Myocytes, Smooth Muscle/pathology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type II/genetics ; Rats ; Rats, Wistar
Chemical Substances	Estrogen Receptor beta ; Interleukin-1beta ; Nitric Oxide (31C4KY9ESH) ; Alloxan (6SW5YHA5NG) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, rat (EC 1.14.13.39)
Language	English
Publishing date	2018-11-14
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2018.11.030
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Article ; Online: Mitochondrial DNA: A new driver for sex differences in spontaneous hypertension.

Echem, Cinthya / Costa, Tiago Januário da / Oliveira, Vanessa / Giglio Colli, Lucas / Landgraf, Maristella Almeida / Rodrigues, Stephen Fernandes / Franco, Maria do Carmo Pinho / Landgraf, Richardt Gama / Santos-Eichler, Rosângela Aparecida / Bomfim, Gisele Facholi / Akamine, Eliana Hiromi / de Carvalho, Maria Helena Catelli

Pharmacological research

2019 Volume 144, Page(s) 142–150

Abstract: The prevalence of arterial hypertension (AH) is higher in men than in premenopausal women of the same age. AH has been characterized as a chronic inflammatory disease and activation of Toll-like receptors (TLR) by damage-associated molecular patterns ( ... ...

Abstract	The prevalence of arterial hypertension (AH) is higher in men than in premenopausal women of the same age. AH has been characterized as a chronic inflammatory disease and activation of Toll-like receptors (TLR) by damage-associated molecular patterns (DAMPs) is involved. Mitochondrial DNA (mtDNA) may be released by end-organ damage, which is recognized and activates TLR9. The serum level of mtDNA is increased in AH. The aim of this study was to compare the serum mtDNA levels between male and female spontaneously hypertensive rats (SHR) and to evaluate the sex differences in the effect of mtDNA on the function, inflammation and signaling pathway related to TLR9 in the vasculature. Male and female 15-week-old SHR and Wistar rats were used to evaluate the arterial blood pressure, serum mtDNA, contractile response, inflammatory markers and signaling pathway related to TLR9. Male SHR had higher arterial blood pressure values and serum mtDNA compared to female SHR and to male and female normotensive Wistar rats. In male SHR aorta, mtDNA incubation increased the contractile response to phenylephrine, which was blunted by inhibition of TLR9, and also increased pro-inflammatory molecules IL-6 and TNF-α. However, in female SHR aorta, mtDNA incubation did not change the contractile response, reduced pro-inflammatory molecules and prevented oxidative stress. mtDNA incubation did not change the expression of TLR9, MyD88 and eNOS neither in male nor in female SHR aorta, but it increased the phosphorylation of ERK1/2 in male and reduced in female SHR aorta. The mtDNA differential modulation of vascular response in male and female SHR might contribute to sex differences in AH. This study contributes to the understanding of a need for more personalized therapeutic strategies for men and women with hypertension. Keywords: Sex differences, Arterial hypertension, Mitochondrial DNA, Toll-Like receptor 9.
MeSH term(s)	Animals ; Arteritis/blood ; Arteritis/etiology ; Arteritis/immunology ; DNA, Mitochondrial/blood ; DNA, Mitochondrial/immunology ; Female ; Hypertension/blood ; Hypertension/etiology ; Hypertension/immunology ; Male ; Rats, Inbred SHR ; Rats, Wistar ; Sex Factors ; Toll-Like Receptor 9/immunology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	DNA, Mitochondrial ; Toll-Like Receptor 9 ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2019-04-06
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2019.04.008
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Article ; Online: Influence of aerobic training on the reduced vasoconstriction to angiotensin II in rats exposed to intrauterine growth restriction: possible role of oxidative stress and AT2 receptor of angiotensin II.

Oliveira, Vanessa / Akamine, Eliana Hiromi / Carvalho, Maria Helena C / Michelini, Lisete Compagno / Fortes, Zuleica Bruno / Cunha, Tatiana Sousa / do Carmo Franco, Maria

PloS one

2014 Volume 9, Issue 11, Page(s) e113035

Abstract: Intrauterine growth restriction (IUGR) is associated with impaired vascular function, which contributes to the increased incidence of chronic disease. The aim of this study was to investigate whether aerobic training improves AngII-induced ... ...

Abstract	Intrauterine growth restriction (IUGR) is associated with impaired vascular function, which contributes to the increased incidence of chronic disease. The aim of this study was to investigate whether aerobic training improves AngII-induced vasoconstriction in IUGR rats. Moreover, we assess the role of superoxide dismutase (SOD) isoforms and NADPH oxidase-derived superoxide anions in this improvement. Female Wistar rats were randomly divided into two groups on day 1 of pregnancy. A control group was fed standard chow ad libitum, and a restricted group was fed 50% of the ad libitum intake throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to 4 experimental groups: sedentary control (SC), trained control (TC), sedentary restricted (SRT), and trained restricted (TRT). The training protocol was performed on a treadmill and consisted of a continuous 60-min session 5 days/week for 10 weeks. Following aerobic training, concentration-response curves to AngII were obtained in endothelium-intact aortic rings. Protein expression of SOD isoforms, AngII receptors and the NADPH oxidase component p47phox was assessed by Western blot analysis. The dihydroethidium was used to evaluate the in situ superoxide levels under basal conditions or in the presence of apocynin, losartan or PD 123,319. Our results indicate that aerobic training can prevent IUGR-associated increases in AngII-dependent vasoconstriction and can restore basal superoxide levels in the aortic rings of TRT rats. Moreover, we observed that aerobic training normalized the increased p47phox protein expression and increased MnSOD and AT2 receptor protein expression in thoracic aortas of SRT rats. In summary, aerobic training can result in an upregulation of antioxidant defense by improved of MnSOD expression and attenuation of NADPH oxidase component p47phox. These effects are accompanied by increased expression of AT2 receptor, which provide positive effects against Ang II-induced superoxide generation, resulting in attenuation of AngII-induced vasoconstriction.
MeSH term(s)	Angiotensin II/metabolism ; Animals ; Female ; Fetal Growth Retardation/physiopathology ; Gene Expression Regulation/physiology ; Male ; NADPH Oxidases/metabolism ; Oxidative Stress/physiology ; Physical Conditioning, Animal/physiology ; Pregnancy ; Rats ; Receptor, Angiotensin, Type 2/metabolism ; Superoxide Dismutase/metabolism ; Vasoconstriction/physiology
Chemical Substances	Receptor, Angiotensin, Type 2 ; Angiotensin II (11128-99-7) ; Superoxide Dismutase (EC 1.15.1.1) ; NADPH Oxidases (EC 1.6.3.-)
Language	English
Publishing date	2014
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0113035
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