Ana M Briones

Ana M Briones
Universidad Autónoma de Madrid | UAM · Department of Pharmacology

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148
Publications
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5,608
Citations
Citations since 2017
37 Research Items
2729 Citations
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500
20172018201920202021202220230100200300400500

Publications

Publications (148)
Article
COVID19 is associated with vascular inflammation. IFN-alpha (IFNα) and IFN-lambda3 (IFNλ3) are potent cytokines produced in viral infections. Their effects involve interferon-stimulated genes (ISGs) and may influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. We hypothesized that S1P-induce...
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In diabetes, chronic hyperglycemia, dyslipidemia, inflammation and oxidative stress contribute to the progression of macro/microvascular complications. Recently, benefits of the use of flavonoids in these conditions have been established. This study investigates, in two different mouse models of diabetes, the vasculoprotective effects of the synthe...
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Background: Resolution of inflammation is orchestrated by specialized pro-resolving mediators (SPMs), and this would be impaired in some cardiovascular diseases. Among SPMs, resolvins (Rv) have beneficial effects in cardiovascular pathologies, but little is known about their effect on cardiovascular damage in hypertension. Methods: Aorta, small...
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Introduction: Vascular functional and structural alterations induced by hypertension are greatly influenced by low- grade chronic inflammation. Resolution of inflammation is orchestrated by specialized lipid pro-resolving mediators (SPMs), which derive from n3 fatty acids (PUFAs). Previous evidence suggest that SPM prevent vascular damage in severa...
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Objective: COVID19-associated immunopathology is associated with increased production of interferon (IFN)-alpha (IFNα) and lambda3 (IFNL3). Effects of IFNs are mediated by interferon-stimulated genes (ISGs) and influence expression of angiotensin-converting enzyme 2 (ACE2), the receptor for S-protein (S1P) of SARS-CoV-2. Increasing evidence indica...
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The modulation of the host's metabolism to protect tissue from damage induces tolerance to infections increasing survival. Here, we examined the role of the thyroid hormones, key metabolic regulators, in the outcome of malaria. Hypothyroidism confers protection to experimental cerebral malaria by a disease tolerance mechanism. Hypothyroid mice disp...
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Vascular remodeling is a typical feature of vascular diseases, such as atherosclerosis, aneurysms or restenosis. Excessive inflammation is a key mechanism underlying vascular remodeling via the modulation of vascular fibrosis, phenotype and function. Recent evidence suggests that not only augmented inflammation but unresolved inflammation might als...
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Background and purpose: Microsomal prostaglandin E synthase-1 (mPGES-1) is an inducible isomerase responsible for prostaglandin E2 production in inflammatory conditions. We evaluated the role of mPGES-1 in obesity development and in the metabolic and cardiovascular alterations associated. Experimental approach: mPGES-1+/+ and mPGES-1-/- mice wer...
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Aims Interferon-stimulated gene 15 (ISG15) encodes a ubiquitin-like protein that induces a reversible post-translational modification (ISGylation) and can also be secreted as a free form. ISG15 plays an essential role as host-defence response to microbial infection; however, its contribution to vascular damage associated with hypertension is unknow...
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Background: Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue caused by mutations in the FBN1 gene encoding a large glycoprotein in the extracellular matrix called fibrillin-1. The major complication of this connective disorder is the risk to develop thoracic aortic aneurysm (TAA). To date, no effective pharmacologica...
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Background and purpose: KV 1.3 potassium channels are expressed in vascular smooth muscle cells (VSMCs), where they contribute to proliferation rather than contraction and participate in vascular remodeling. KV 1.3 channels are also expressed in macrophages, where they assemble with KV 1.5 channels (KV 1.3/KV 1.5), whose activation generates a KV...
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No drug therapy has shown to limit abdominal aortic aneurysm (AAA) growth or rupture, and the understanding of the disease biology is incomplete; whereby, one challenge of vascular medicine is the development of good animal models and therapies for this life-threatening condition. The nuclear receptor NOR-1 (neuron-derived orphan receptor 1) contro...
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Perivascular adipose tissue (PVAT) is increasingly being regarded as an important endocrine organ that directly impacts vessel function, structure, and contractility in obesity-associated diseases. We uncover here a role for myeloid G protein-coupled receptor kinase 2 (GRK2) in the modulation of PVAT-dependent vasodilation responses. GRK2 expressio...
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Objective microRNAs are master regulators of gene expression with essential roles in virtually all biological processes. miR-217 has been associated with aging and cellular senescence, but its role in vascular disease is not understood. Approach and Results We have used an inducible endothelium-specific knock-in mouse model to address the role of...
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Antioxidant compounds, including polyphenols, have therapeutic effects because of their anti-inflammatory, antihypertensive, antithrombotic and antiproliferative properties. They play important roles in protecting the cardiovascular and neurological systems, by having preventive or protective effects against free radicals produced by either normal...
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An important link exists between hypertension and inflammation. Hypertensive patients present elevated circulating levels of proinflammatory cytokines, including interleukin-17A (IL-17A). This cytokine participates in host defense, autoimmune and chronic inflammatory pathologies, and cardiovascular diseases, mainly through the regulation of proinfl...
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Endothelin-1 (ET-1) is an important modulator of the vascular tone and a proinflammatory molecule that contributes to the vascular damage observed in hypertension. Peroxisome-proliferator activated receptors-γ (PPARγ) agonists show cardioprotective properties by decreasing inflammatory molecules such as COX-2 and reactive oxygen species (ROS), amon...
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Organ regeneration is preceded by the recruitment of innate immune cells, which play an active role during repair and regrowth. Here, we studied macrophage subtypes during organ regeneration in the zebrafish, an animal model with a high regenerative capacity. We identified a macrophage subpopulation expressing Wilms tumor 1b (wt1b), which accumulat...
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Vascular stiffness is a major cause of cardiovascular disease during normal aging and in Hutchinson–Gilford progeria syndrome (HGPS), a rare genetic disorder caused by ubiquitous progerin expression. This mutant form of lamin A causes premature aging associated with cardiovascular alterations that lead to death at an average age of 14.6 years. We i...
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G protein-coupled receptor kinase 2 (GRK2) is a central signaling node involved in the modulation of many G protein-coupled receptors (GPCRs) and also displaying regulatory functions in other cell signaling routes. GRK2 levels and activity have been reported to be enhanced in patients or in preclinical models of several relevant pathological situat...
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Branched‐chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cel...
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mPGES-1 (microsomal prostaglandin E synthase-1), the downstream enzyme responsible for PGE2 (prostaglandin E2) synthesis in inflammatory conditions and oxidative stress are increased in vessels from hypertensive animals. We evaluated the role of mPGES-1-derived PGE2 in the vascular dysfunction and remodeling in hypertension and the possible contrib...
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Cyclooxygenase-2 (COX-2) derived-prostanoids participate in the altered vascular function and mechanical properties in cardiovascular diseases. We investigated whether regulator of calcineurin 1 (Rcan1) participates in vascular contractility and stiffness through the regulation of COX-2. For this, wild type (Rcan1+/+) and Rcan1-deficient (Rcan1-/-)...
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Introduction Lysyl oxidase (LOX) participates in the assembly of collagen and elastin fibres. The impact of vascular LOX over-expression on extracellular matrix (ECM) structure and its contribution to oxidative stress has been analysed. Methods Studies were conducted on mice over-expressing LOX (Tg), specifically in smooth muscle cells (VSMC). Gen...
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Introduction: Lysyl oxidase (LOX) participates in the assembly of collagen and elastin fibres. The impact of vascular LOX over-expression on extracellular matrix (ECM) structure and its contribution to oxidative stress has been analysed. Methods: Studies were conducted on mice over-expressing LOX (Tg), specifically in smooth muscle cells (VSMC)....
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G protein-coupled receptor kinase 2 (GRK2) is emerging as a pivotal signalling hub able to integrate different transduction cascades. This ability appears to underlie its central role in different physiological and pathological conditions. Key mediators of cardiovascular function (such as catecholamines or angiotensin II) and components of the syst...
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The study of adipose tissue and more specifically of adipocytes is considered pivotal for dissecting molecular mechanisms responsible for alterations in several organs and systems, including adipose tissue, not only in obesity but also in other diseases (hypertension, heart failure). Adipose tissue is a complex tissue composed of adipocytes and the...
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Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show...
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Reactive oxygen species (ROS) are key signaling molecules that regulate vascular function and structure in physiological conditions. A misbalance between the production and detoxification of ROS increases oxidative stress that is involved in the vascular remodeling associated with cardiovascular diseases such as hypertension by affecting inflammati...
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High doses of AngII receptor (AT1R) blockers (ARBs) are reno-protective in diabetes. Underlying mechanisms remain unclear. We evaluated whether high/ultra-high doses of candesartan (ARB) upregulate ACE2/Ang II type 2 receptor (AT2R)/Mas receptor (protective axis of the of the renin-angiotensin-system (RAS)) in diabetic mice. Systolic blood pressure...
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PPARβ/δ activation protects against endothelial dysfunction in diabetic models. Elevated glucose is known to impair cAMP-induced relaxation and Kv channel function in coronary arteries (CA). Herein, we aimed to analyse the possible protective effects of the PPARβ/δ agonist GW0742 on the hyperglycemic-induced impairment of cAMP-induced relaxation an...
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Objective: NOX-1 and NOX-4 are key enzymes responsible for reactive oxygen species (ROS) generation in vascular smooth muscle cells (VSMC). The RNA-binding protein Hu antigen R (HuR) is implicated in posttranscriptional regulation of gene expression; however, its role regulating NOX is unknown. We investigated transcriptional and posttranscription...
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Obesity is a worldwide problem that has reached epidemic proportions both in developed and developing countries. The excessive accumulation of fat poses a risk to health since it favours the development of metabolic alterations including insulin resistance and tissue inflammation, which further contribute to the progress of the complex pathological...
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Fatty acids cause endothelial dysfunction involving increased ROS (reactive oxygen species) and reduced NO (nitric oxide) bioavailability. We show that in MAECs (mouse aortic endothelial cells), the PPARβ/δ (peroxisome- proliferator-activated receptor β/δ) agonist GW0742 prevented the decreased A23187-stimulated NO production, phosphorylation of eN...
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Interleukin-33 (IL-33) but not soluble ST2 (sST2) exerts anti-inflammatory and protective effects in several tissues. Aldosterone, a proinflammatory mediator which promotes adipogenesis, is elevated in obese patients. The aim of this study was to investigate the interactions between IL-33/ST2 system and Aldosterone in adipose tissue. Rats fed a hig...
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TLR4 signalling contributes to inflammatory cardiovascular diseases, but little is known about its role in hypertension and the associated vascular damage. We investigated whether TLR4 activation contributes to angiotensin II (AngII)-induced hypertension and the associated vascular structural, mechanical and functional alterations. We used aorta an...
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Hypertension is a major cardiovascular risk factor. Of the many processes involved in the pathophysiology of hypertension, vascular damage due to oxidative stress (excess bioavailability of reactive oxygen species [ROS]) is particularly important. Physiologically, ROS regulate vascular function through redox-sensitive signalling pathways. In hypert...
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BACKGROUND AND PURPOSE: Angiotensin II (AngII) and interleukin 1β (IL-1β) are involved in cardiovascular diseases through induction of inflammatory pathways. HuR is an ARE-binding protein that contributes to the mRNA stabilization of many genes. This study investigated the contribution of HuR upon COX-2 expression induced by AngII and IL-1β and its...
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Chronic exposure to low lead concentration produces hypertension; however, the underlying mechanisms remain unclear. We analyzed the role of oxidative stress, cyclooxygenase-2-dependent pathways and MAPK in the vascular alterations induced by chronic lead exposure. Aortas from lead-treated Wistar rats (1st dose: 10μg/100g; subsequent doses: 0.125μg...
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Reactive oxygen species (ROS) are reactive derivatives of O2 metabolism produced by all types of vascular cells. ROS play an important role in both physiological and pathological situations by acting as intracellular signaling molecules which regulate vascular function and structure. Accordingly, oxidative stress is implicated among other processes...
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Aim: : The aim of this study was to analyse the signalling pathways involved in H2O2 vascular responses in hypertension. Methods: Vascular function, thromboxane A2 (TXA2) production, oxidative stress and protein expression were determined in mesenteric resistance arteries (MRAs) from hypertensive (spontaneously hypertensive rats, SHR) and normot...
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Aims: Connective tissue growth factor (CTGF/CCN2) is a developmental gene upregulated in pathological conditions, including cardiovascular diseases, whose product is a matricellular protein that can be degraded to biologically active fragments. Among them, the C-terminal module IV [CCN2(IV)] regulates many cellular functions, but there are no data...
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Purpose. Angiotensin II (Ang II) and interleukin 1b (IL-1β) are involved in cardiovascular diseases inducing pro-inflammatory enzymes such as cyclooxygenase 2 (COX-2). COX-2 is an early response gene regulated by its transcription and by mRNA stability. Our purpose was to evaluate whether Ang II potentiates the effect of IL-1β on COX-2 expression a...
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Purpose. The NADPH oxidase (NOX) is the main source of reactive oxygen species (ROS) which are important in vascular remodeling. Interleukin 1b (IL-1β) and angiotensin II (Ang II) induce different NOX isoforms. We assessed the effects of IL-1β and Ang II on NOX-1 and NOX-4 expression, NOX activity and ROS production, the mechanisms involved and the...
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Microvascular abnormalities, both in function and structure, lead to impaired tissue perfusion that may affect multiple tissues and organs and seem to be involved in target-organ damage and complications observed in obesity and insulin resistance. In general, vascular remodeling of small arteries associated to cardiometabolic diseases seems to be h...
Article
C5-unsubstituted-C6-aryl-1,4-dihydropyridines were prepared by a CAN-catalyzed multicomponent reaction from chalcones, β-dicarbonyl compounds and ammonium acetate. These compounds were able to block Ca(2+) entry after a depolarizing stimulus and showed an improved CaV1.3/CaV1.2 selectivity in comparison with nifedipine. Furthermore, they were able...
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Elevated production of prostanoids from the constitutive (COX-1) or inducible (COX-2) cyclo-oxygenases has been involved in the alterations in vascular function, structure and mechanical properties observed in cardiovascular diseases, including hypertension. In addition, it is well known that production of ROS (reactive oxygen species) plays an imp...
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G protein-coupled receptor kinase 2 (GRK2) is a ubiquitous serine/threonine protein kinase able to phosphorylate and desensitize the active form of several G protein-coupled receptors. Given the lack of selective inhibitors for GRK2, we investigated the effects elicited by GRK2 inhibition in vascular responses using global adult hemizygous mice (GR...
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Mercury exposure is known to increase cardiovascular risk but the underlying cellular mechanisms remain undetermined. We analyzed whether chronic exposure to HgCl2 affects vascular structure and the functional properties of vascular smooth muscle cells (VSMC) through oxidative stress/cyclooxygenase-2 dependent pathways. Mesenteric resistance arteri...
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The regular practice of physical activity is a well-recommended strategy for the prevention and treatment of several cardiovascular and metabolic diseases. Physical exercise prevents the progression of vascular diseases and reduces cardiovascular morbidity and mortality. Exercise training also ameliorates vascular changes including endothelial dysf...
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Unlabelled: Mercury increases the risk of cardiovascular disease and oxidative stress and alters vascular reactivity. This metal elicits endothelial dysfunction causing decreased NO bioavailability via increased oxidative stress and contractile prostanoid production. NADPH oxidase is the major source of reactive oxygen species (ROS) in the vascula...
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Background and purpose: Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. We investigated the effects of aerobic exercise training in vascular remodelling and in the mechanical and functional alterations of coronary and small mesenteric arteries from spontaneously hypertensive rats (S...
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The renin-angiotensin system (RAS) plays a pivotal role in the pathophysiology of cardiovascular and kidney disease. Protection against kidney injury has been evidenced by high dose angiotensin II (Ang II) type 1 receptor (AT1R) blockers. In this study we sought to determine whether a high dose of candesartan has renoprotective actions associated w...
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Aims: This study evaluates a possible relationship between reactive oxygen species (ROS) and cyclooxygenase (COX)-2-derived products in conductance and resistance arteries from hypertensive animals. Angiotensin II (Ang II)-infused mice or spontaneously hypertensive rats treated with the NAD(P)H Oxidase inhibitor apocynin, the mitochondrion-targete...
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We reported aldosterone as a novel adipocyte-derived factor that regulates vascular function. We aimed to investigate molecular mechanisms, signaling pathways, and functional significance of adipocyte-derived aldosterone and to test whether adipocyte-derived aldosterone is increased in diabetes mellitus-associated obesity, which contributes to vasc...
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PPARγ agonists, glitazones, have cardioprotective and anti-inflammatory actions associated with gene transcription interference. In this study, we determined whether chronic treatment of adult spontaneously hypertensive rats (SHR) with pioglitazone alters BP and vascular structure and function, and the possible mechanisms involved. Mesenteric resis...
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Hypertension is associated with increased plasma inflammatory markers such as cytokines and increased vascular cyclooxygenase-2 (COX-2) expression. The ability of peroxisome proliferator-activated receptor-γ (PPARγ) agonists to reduce oxidative stress seems to contribute to their anti-inflammatory properties. This study analyzes the effect of piogl...
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Adipose tissue influences vascular function through adipocyte-derived factors, including components of the renin-angiotensin-aldosterone system. Molecular mechanisms underlying these phenomena are elusive. We investigated the role of adipocyte-derived factors on mitogen-activated protein kinases (MAPKs), proinflammatory status, apoptosis, and mitog...
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We demonstrated c-Src activation as a novel non-genomic signalling pathway for aldosterone in vascular smooth muscle cells (VSMCs). Here, we investigated molecular mechanisms and biological responses of this phenomenon, focusing on the role of lipid rafts/caveolae and platelet-derived growth factor receptor (PDGFR) in c-Src-regulated proinflammator...
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Liver growth factor (LGF) is an endogenous albumin-bilirubin complex with antihypertensive effects in spontaneously hypertensive rats (SHR). We assessed the actions of LGF treatment on SHR mesenteric resistance and intramyocardial arteries (MRA and IMA, respectively), heart, and vascular smooth muscle cells (VSMC). SHR and Wistar-Kyoto (WKY) rats t...
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The functional significance and regulation of NAD(P)H oxidase (Nox) isoforms by angiotensin II (Ang II) and endothelin-1 (ET-1) in vascular smooth muscle cells (VSMCs) from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) was studied. Expression of Nox1, Nox2, and Nox4 (gene and protein) and NAD(P)H oxidase activity were in...
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Reactive oxygen species (ROS) are important mediators of cell growth, adhesion, differentiation, migration, senescence, and apoptosis. ROS play an important physiological role in regulating vascular tone and can also contribute to pathological mechanisms related to endothelial dysfunction, vascular reactivity, arterial remodeling, and vascular infl...