scholarly journals Vascular and Central Activation of Peroxisome Proliferator-Activated Receptor-  Attenuates Angiotensin II-Induced Hypertension: Role of RGS-5

2016 ◽  
Vol 358 (1) ◽  
pp. 151-163 ◽  
Author(s):  
M. Romero ◽  
R. Jimenez ◽  
M. Toral ◽  
E. Leon-Gomez ◽  
M. Gomez-Guzman ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Central Activation ◽  
Induced Hypertension

scholarly journals Peroxisome Proliferator Activated Receptor-αAgonist Slows the Progression of Hypertension, Attenuates Plasma Interleukin-6 Levels and Renal Inflammatory Markers in Angiotensin II Infused Mice

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Justin L. Wilson ◽  
Rong Duan ◽  
Ahmed El-Marakby ◽  
Abdulmohsin Alhashim ◽  
Dexter L. Lee
Keyword(s):  
Angiotensin Ii ◽  
Inflammatory Markers ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Induced Hypertension ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Renal Expression

The anti-inflammatory properties of PPAR-αplays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-αagonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-αKO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-αKO mice compared to WT (161±4 mmHg versus145±4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134±7 mmHg). Plasma IL-6 levels were higher in PPAR-αKO mice on day 12 of Ang II infusion (30±4versus8±2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treated WT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1, MCP-1 and COX-2 in WT + Ang II mice. Our results demonstrate that activation of PPAR-αattenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.

Stretch reduces nephrin expression via an angiotensin II-AT1-dependent mechanism in human podocytes: effect of rosiglitazone

2010 ◽  
Vol 298 (2) ◽  
pp. F381-F390 ◽  
Author(s):  
Ilaria Miceli ◽  
Davina Burt ◽  
Elena Tarabra ◽  
Giovanni Camussi ◽  
Paolo Cavallo Perin ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Slit Diaphragm ◽  
Peroxisome Proliferator ◽  
Glomerular Permeability ◽  
Receptor System ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Mrna And Protein Expression

Increased glomerular permeability to proteins is a characteristic feature of diabetic nephropathy (DN). The slit diaphragm is the major restriction site to protein filtration, and the loss of nephrin, a key component of the slit diaphragm, has been demonstrated in both human and experimental DN. Both systemic and glomerular hypertension are believed to be important in the pathogenesis of DN. Human immortalized podocytes were subjected to repeated stretch-relaxation cycles by mechanical deformation with the use of a stress unit (10% elongation, 60 cycles/min) in the presence or absence of candesartan (1 μM), PD-123319 (1 μM), and rosiglitazone (0.1 μM). Nephrin mRNA and protein expression were assessed using quantitative real-time PCR, immunoblotting, and immunofluorescence, and the protein expression of AT1 receptor and angiotensin II secretion were evaluated. Exposure to stretch induced a significant ∼50% decrease in both nephrin mRNA and protein expression. This effect was mediated by an angiotensin II-AT1 mechanism. Indeed, podocyte stretching induced both angiotensin II secretion and AT1 receptor overexpression, podocyte exposure to angiotensin II reduced nephrin protein expression, and both the AT-1 receptor antagonist candesartan and a specific anti-angiotensin II antibody completely abolished stretch-induced nephrin downregulation. Similar to candesartan, the peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, also inhibited stretch-induced nephrin downregulation, suggesting interference with stretch-induced activation of the angiotensin II-AT1 receptor system. Accordingly, rosiglitazone did not alter stretch-induced angiotensin II secretion, but it prevented AT1 upregulation in response to stretch. These results suggest a role for hemodynamic stress in loss of nephrin expression and allude to a role of PPAR-γ agonists in the prevention of this loss.

Abstract P118: Angiotensin Ii Hypertension-dependent Decrease In Circadian Rhythms Of Cardiovascular Parameters: Role Of Peroxisome Proliferator Activated Receptor-α

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Dexter L Lee ◽  
Sheree M Johnson ◽  
Ian Stukes ◽  
Nia Williams ◽  
Ugoeze C Ananaba ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Circadian Rhythms ◽  
Diastolic Pressure ◽  
Interleukin 17 ◽  
Peroxisome Proliferator ◽  
Ang Ii ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cardiovascular Parameters ◽  
Nitrite Nitrate

Decreases in circadian rhythms of cardiovascular parameters, such as day to night changes in mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), systolic (SP) and diastolic pressure (DP) are an index of cardiovascular disease. Peroxisome proliferator activated receptor - alpha (PPAR-α) has been shown to decrease inflammatory markers and hypertension a slow pressor dose of Angiotensin II (Ang II); however, the role of PPAR-α on cardiovascular parameters during the initial stages of Ang II infusion is unknown. We hypothesize that the absence of PPAR-α will cause a reduction in the day to night changes in MAP, HR, PP, SP and DP during the initial stages of a slow pressor dose of Ang II. Male (10 - 12 weeks old) PPAR-αknockout (KO) and wild-type (WT) mice were infused with Ang II (400 ng/kg/min) for three days. Radiotelemetry was used to measure the cardiovascular parameters. The baseline MAP values were: 100 + 10 mmHg (WT) and 108 + 9 mmHg for KO. The baseline HR values were: 530 + 10 bpm (WT) and 526 + 6 bpm (KO). The baseline PPs were 17 + 0.2 mmHg (WT) and 18 + 0.3 mmHg (KO). The baseline SBPs were 108 + 9 mmHg (WT) and 116 + 10 mmHg (KO). The baseline DBPs were 91 + 9 mmHg (WT) and 98 + 10 mmHg (KO). During the first three days of Ang II infusion, the change in day to night MAP was 20 ± 2 mmHg and 10 ± 2 mmHg in Ang II treated WT and KO mice, respectively. Changes in day to night HR were 25 ± 4 bpm and 46 ± 7 bpm for WT and KO mice, respectively. The day to night changes in PP were 8 ± 1 mmHg for WT and 2 ± 2 mmHg for KO mice. The day to night changes in SBPs were 20 ± 2 mmHg and 12 ± 3 mmHg for WT and KO mice, respectively. Changes in day to night DBPs were 18 ± 2 mmHg for WT and 9 ± 2 mmHg for KO mice. TBARS and Interleukin-17 were increased in heart homogenates of KO + Ang II (15 ± 2 μM) and (1.5 ± 0.3 ng/mL) vs WT + Ang II (11 ± 3 μM) and (1.0 ± 0.2 ng/mL). Nitrite/Nitrate was decreased in KO + Ang II (1.0 ± 0.1 nM) vs WT + Ang II (1.5 ± 0.5 nM). In summary, the absence of PPAR-α decreases the day to night changes in MAP, SBP, DBP and PP during the initial three days of a slow pressor dose of Ang II. In the absence of PPAR-α, increases in oxidative stress and inflammation are mechanisms that may contribute to the changes in the cardiovascular parameters and suggest the occurrence of cardiovascular diseases during a slow pressor dose of Ang II-infusion.

scholarly journals Role of macrophage PPARγ in experimental hypertension

2014 ◽  
Vol 306 (1) ◽  
pp. H26-H32 ◽  
Author(s):  
Tamas Kriska ◽  
Cody Cepura ◽  
Kathryn M. Gauthier ◽  
William B. Campbell
Keyword(s):  
Primary Source ◽  
Underlying Mechanism ◽  
Peritoneal Macrophages ◽  
Experimental Hypertension ◽  
Peroxisome Proliferator ◽  
Targeted Disruption ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Induced Hypertension

Targeted disruption of the Alox15 gene makes mice resistant to angiotensin II-, DOCA/salt-, and Nω-nitro-l-arginine methyl ester (l-NAME)-induced experimental hypertension. Macrophages, a primary source of Alox15, are facilitating this resistance, but the underlying mechanism is not known. Because Alox15 metabolites are peroxisome proliferator-activated receptor (PPAR)γ agonists, we hypothesized that activation of macrophage PPARγ is the key step in Alox15 mediation of hypertension. Thioglycollate, used for macrophage elicitation, selectively upregulated PPARγ and its target gene CD36 in peritoneal macrophages of both wild-type (WT) and Alox15−/− mice. Moreover, thioglycollate-injected Alox15−/− mice became hypertensive upon l-NAME treatment. A similar hypertensive effect was observed with adoptive transfer of thioglycollate-elicited Alox15−/− macrophages into Alox15−/− recipient mice. The role of PPARγ was further specified by using the selective PPARγ antagonist GW9662. WT mice treated with 50 μg/kg daily dose of GW9662 for 12 days became resistant to l-NAME-induced hypertension. The PPARγ antagonist treatment also prevented l-NAME-induced hypertension in thioglycollate-injected Alox15−/− mice, indicating a PPARγ-mediated effect in macrophage elicitation and the resultant hypertension. These results indicate a regulatory role for macrophage-localized PPARγ in l-NAME-induced experimental hypertension.

The emerging role of COX-2, 15-LOX, and PPARγ in metabolic diseases and cancer: An introduction to novel multi-target directed ligands (MTDLs)

2020 ◽  
Vol 27 ◽  
Author(s):  
Rana A. Alaaeddine ◽  
Perihan A. Elzahhar ◽  
Ibrahim AlZaim ◽  
Wassim Abou-Kheir ◽  
Ahmed S.F. Belal ◽  
...  
Keyword(s):  
Metabolic Diseases ◽  
Biological Effects ◽  
Arachidonic Acid Metabolism ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cellular Targets ◽  
Design And Synthesis ◽  
Early Results ◽  
Cox 2

: Emerging evidence supports an intertwining framework for the involvement of different inflammatory pathways in a common pathological background for a number of disorders. Of importance are pathways involving arachidonic acid metabolism by cyclooxygenase-2 (COX-2) and 15-lipoxygenase (15-LOX). Both enzyme activities and their products are implicated in a range of pathophysiological processes encompassing metabolic impairment leading to adipose inflammation and the subsequent vascular and neurological disorders, in addition to various pro-and anti-tumorigenic effects. A further layer of complexity is encountered by the disparate, and often reciprocal, modulatory effect COX-2 and 15-LOX activities and metabolites exert on each other or on other cellular targets, the most prominent of which is peroxisome proliferator-activated receptor gamma (PPARγ). Thus, effective therapeutic intervention with such multifaceted disorders requires the simultaneous modulation of more than one target. Here, we describe the role of COX-2, 15-LOX, and PPARγ in cancer and complications of metabolic disorders, highlight the value of designing multi-target directed ligands (MTDLs) modifying their activity, and summarize the available literature regarding the rationale and feasibility of design and synthesis of these ligands together with their known biological effects. We speculate on the potential impact of MTDLs in these disorders as well as emphasize the need for structured future effort to translate these early results facilitating the adoption of these, and similar, molecules in clinical research.

scholarly journals The Nutraceutical N-Palmitoylethanolamide (PEA) Reveals Widespread Molecular Effects Unmasking New Therapeutic Targets in Murine Varicocele

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 734
Author(s):  
Pietro Antonuccio ◽  
Herbert Ryan Marini ◽  
Antonio Micali ◽  
Carmelo Romeo ◽  
Roberta Granese ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Therapeutic Targets ◽  
Sham Operation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pyrin Domain ◽  
Age Related ◽  
Extracellular Signal ◽  
Morphometric Assessment

Varicocele is an age-related disease with no current medical treatments positively impacting infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. The role of peroxisome proliferator-activated receptor-α (PPAR-α), a nuclear receptor, in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors’ roles were investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10 mg/kg i.p.) for 21 days. Another group (WT, PPAR-α KO, and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10 mg/kg i.p.) for 21 days. At the end of treatments, all animals were euthanized. Both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin, and claudin-11 immunohistochemistry and for PPAR-α, TLR4, transforming growth factor-beta3 (TGF-β3), phospho-extracellular signal-Regulated-Kinase (p-ERK) 1/2, and nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain-containing 3 (NLRP3) Western blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology, unmasking new nutraceutical therapeutic targets for future varicocele research and supporting surgical management of male infertility.

scholarly journals From Exercise to Cognitive Performance: Role of Irisin

2021 ◽  
Vol 11 (15) ◽  
pp. 7120
Author(s):  
Mirko Pesce ◽  
Irene La Fratta ◽  
Teresa Paolucci ◽  
Alfredo Grilli ◽  
Antonia Patruno ◽  
...  
Keyword(s):  
The Elderly ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Beneficial Effects ◽  
General Exercise ◽  
Fibronectin Type Iii ◽  
Exercise Induced ◽  
Fibronectin Type Iii Domain ◽  
The Brain

The beneficial effects of exercise on the brain are well known. In general, exercise offers an effective way to improve cognitive function in all ages, particularly in the elderly, who are considered the most vulnerable to neurodegenerative disorders. In this regard, myokines, hormones secreted by muscle in response to exercise, have recently gained attention as beneficial mediators. Irisin is a novel exercise-induced myokine, that modulates several bodily processes, such as glucose homeostasis, and reduces systemic inflammation. Irisin is cleaved from fibronectin type III domain containing 5 (FNDC5), a transmembrane precursor protein expressed in muscle under the control of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α). The FNDC5/irisin system is also expressed in the hippocampus, where it stimulates the expression of the neurotrophin brain-derived neurotrophic factor in this area that is associated with learning and memory. In this review, we aimed to discuss the role of irisin as a key mediator of the beneficial effects of exercise on synaptic plasticity and memory in the elderly, suggesting its roles within the main promoters of the beneficial effects of exercise on the brain.

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