scholarly journals Early manifestation of aging-related vascular dysfunction in human penile vasculature—A potential explanation for the role of erectile dysfunction as a harbinger of systemic vascular disease

GeroScience ◽  
2021 ◽  
Author(s):  
Mariam El Assar ◽  
Javier Angulo ◽  
Esther García-Rojo ◽  
Alejandro Sevilleja-Ortiz ◽  
Borja García-Gómez ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Potential Explanation ◽  
Early Manifestation

scholarly journals Vascular Disease in Diabetic Women: Why Do They Miss the Female Protection?

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ana Paula Villela Dantas ◽  
Zuleica Bruno Fortes ◽  
Maria Helena Catelli de Carvalho
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Protective Effects ◽  
Vascular Protection

Gender plays a pivotal role in the onset as well as in the progression of the cardiovascular disease with a higher morbidity and mortality being detected in men with respect to women. Type 2 Diabetes Mellitus (T2DM) may reduce gender-related differences in the prevalence of cardiovascular disease by fading the vascular protective effects afforded by estrogen in females. This article will discuss the role of sex and sex hormones on the incidence and mechanisms involved in vascular dysfunction associated to T2DM, which might explain why women with T2DM lack the vascular protection.

Abstract T MP114: PPARγ in Endothelial Cells Plays an Essential Role in Protecting Against Vascular Aging: Role of Oxidative Stress and Rho Kinase

Stroke ◽  
2014 ◽  
Vol 45 (suppl_1) ◽  
Author(s):  
Dale Kinzenbaw ◽  
T. Micheal De Silva ◽  
Curt Sigmund ◽  
Frank M Faraci
Keyword(s):  
Oxidative Stress ◽  
Endothelial Function ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Rho Kinase ◽  
Dominant Negative ◽  
Vascular Aging ◽  
Dominant Negative Mutation ◽  
Age Related

Although aging is the greatest risk factor for vascular disease and stroke, relatively little is known regarding mechanisms that regulate vascular aging. Endothelial dysfunction - a key element of carotid artery and cerebrovascular disease - progresses with age, greatly increasing the risk for ischemic stroke and cognitive impairment. The nuclear receptor peroxisome proliferator activated receptor-γ (PPARγ) is a ligand-activated transcription factor that may exert diverse effects depending on the cell type. Because little is known regarding the role of PPARγ in vascular aging, we used transgenic mice expressing a dominant negative mutation in human PPARγ (V290M) under control of the endothelial-specific vascular cadherin promoter (designated E-V290M) to examine the hypothesis that cell-specific interference with PPARγ would promote age-induced vascular dysfunction. Responses of carotid arteries from adult (11-12 mo) and old (24±1 mo) E-V290M mice and non-transgenic littermates were examined in vitro. Acetylcholine (an endothelium-dependent agonist) produced similar relaxation of arteries from adult control and E-V290M mice as well as old control mice. In contrast, responses to acetylcholine in arteries from old E-V290M mice were reduced by more than 50% in old E-V290M mice (P<0.01). Endothelial function in old E-V290M mice was not altered by indomethacin but was restored to normal by tempol (a superoxide scavenger) or VAS-2870 (an inhibitor of NADPH oxidase). Reactive oxygen species can activate Rho kinase (a potential mediator of vascular disease) and inhibition of Rho kinase with Y-27632 restored endothelial function to normal in old E-V290M mice. Relaxation of arteries to nitroprusside, which acts directly on vascular muscle, was similar in all groups. These findings provide the first evidence that age-related vascular dysfunction is accelerated following cell-specific interference with endothelial PPARγ through mechanisms involving oxidative stress and Rho kinase. This novel role for endothelial PPARγ has implications for understanding vascular pathophysiology as well as therapeutic approaches for age-induced large and small vessel disease.

Abstract 610: Context-Dependent Effects of Suppressor of Cytokine Signaling 3 (SOCS3) in Angiotensin II-Induced Vascular Dysfunction: Mechanisms and Role of Bone Marrow-Derived Cells

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Ying Li ◽  
Dale Kinzenbaw ◽  
Mary Modrick ◽  
Lecia Epping ◽  
John T Harty ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Vascular Disease ◽  
Vascular Dysfunction ◽  
Pressor Response ◽  
Ang Ii ◽  
Bone Marrow Derived Cells ◽  
The Impact

Angiotensin II (Ang II) promotes vascular disease and hypertension, in part, by activating the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway. Although SOCS3 regulates this pathway in the immune system, its role in vascular disease and hypertension is unknown. In this study, we investigated the role of SOCS3 in a model of Ang II-induced vascular disease. To exam direct effects, carotid arteries from wild-type (WT) and SOCS3 haplodeficient (SOCS3 +/- ) mice were incubated with Ang II for 22 hrs, followed by examination of endothelial function using acetylcholine (Ach). Relaxation to Ach was similar in all arteries incubated with vehicle. A low concentration of Ang II (1 nmol/L) did not affect Ach-induced vasodilation in WT mice, but reduced that of SOCS3 +/- mice by ~50% (P<0.05). Ang II-induced impairment was prevented by inhibitors of STAT3, IL-6, NF-κB, or a scavenger of superoxide. Responses to nitroprusside were similar in all groups. We also tested the impact of SOCS3 in vivo by systemically infusing Ang II (1.4 mg/kg per day) for 14 days via osmotic mini-pumps. Ach-induced vasodilation in carotid and resistance arteries in brain from WT mice was reduced by ~60% (P<0.05). Surprisingly, deficiency in SOCS3 prevented the majority of Ang II-induced endothelial dysfunction without affecting the pressor response to Ang II. Lethally irradiated WT mice reconstituted with SOCS3 +/- bone marrow were protected from Ang II-induced endothelial dysfunction (P<0.05), while reconstitution of irradiated SOCS3 +/- mice with WT bone marrow exacerbated Ang II-induced vascular dysfunction (P<0.05). WT into WT and SOCS3 +/- into SOCS3 +/- bone marrow chimeras exhibited vascular function consistent with non-irradiated controls. The pressor response to Ang II was reduced by ~50% in WT mice reconstituted with bone marrow from SOCS3 +/- mice (P<0.05). These data suggest SOCS3 exerts divergent local versus systemic effects on Ang II-induced vascular dysfunction. In the face of SOCS3 deficiency, bone marrow-derived cells protect against Ang II-induced vascular dysfunction and hypertension.

Role of Methylglyoxal in Diabetic Cardiovascular and Kidney Diseases: Insights from Basic Science for Application into Clinical Practice

2018 ◽  
Vol 24 (26) ◽  
pp. 3072-3083 ◽  
Author(s):  
Sowndramalingam Sankaralingam ◽  
Angham Ibrahim ◽  
MD Mizanur Rahman ◽  
Ali H. Eid ◽  
Shankar Munusamy
Keyword(s):  
Therapeutic Strategy ◽  
Kidney Diseases ◽  
Vascular Dysfunction ◽  
Dicarbonyl Compound ◽  
Renal Complications ◽  
Lysine Residues ◽  
Patients With Diabetes ◽  
Prevalence Of Diabetes Mellitus

Background: The incidence and prevalence of diabetes mellitus are increasing globally at alarming rates. Cardiovascular and renal complications are the major cause of morbidity and mortality in patients with diabetes. Methylglyoxal (MG) - a highly reactive dicarbonyl compound – is increased in patients with diabetes and has been implicated to play a detrimental role in the etiology of cardiovascular and renal complications. Derived from glucose, MG binds to arginine and lysine residues in proteins, and the resultant end products serve as surrogate markers of MG generation in vivo. Under normal conditions, MG is detoxified by the enzyme glyoxalase 1 (Glo1), using reduced glutathione as a co-factor. Elevated levels of MG is known to cause endothelial and vascular dysfunction, oxidative stress and atherosclerosis; all of which are risk factors for cardiovascular diseases. Moreover, MG has also been shown to cause pathologic structural alterations and impair kidney function. Conversely, MG scavengers (such as N-acetylcysteine, aminoguanidine or metformin) or Nrf2/Glo1 activators (such as trans-resveratrol / hesperetin) are shown to be useful in preventing MG-induced cardiovascular and renal complications in diabetes. However, clinical evidence supporting the MG lowering properties of these agents are limited and hence, need further investigation. Conclusion: Reducing MG levels directly using scavengers or indirectly via activation of Nrf2/Glo1 may serve as a novel and potent therapeutic strategy to counter the deleterious effects of MG in diabetic complications.

Diabetes and Vascular Disease: Is It All About Glycemia?

2019 ◽  
Vol 25 (29) ◽  
pp. 3112-3127 ◽  
Author(s):  
Alessandra Vecchié ◽  
Fabrizio Montecucco ◽  
Federico Carbone ◽  
Franco Dallegri ◽  
Aldo Bonaventura
Keyword(s):  
Vascular Disease ◽  
Inflammatory Cell ◽  
Vascular Dysfunction ◽  
Microvascular Complications ◽  
Coagulation Cascade ◽  
Inflammatory Cell Infiltrate ◽  
Extracellular Traps ◽  
Thrombotic Complications ◽  
Independent Entity ◽  
Complications And Mortality

Background: Diabetes is increasing over time, mainly driven by obesity, aging, and urbanization. Classical macro- and microvascular complications represent the final result of a complex interplay involving atherosclerosis at all stages. Methods: In this review, we aim at focusing on current updates in the pathophysiology of vascular disease in diabetes and discussing how new therapies might influence the management of these patients at high cardiovascular risk. Diabetes shows accelerated atherosclerosis with a larger inflammatory cell infiltrate, thus favoring the development of heart failure. ‘Diabetic cardiomyopathy’ perfectly describes a specific ischemia- and hypertension- independent entity due to diabetes-related metabolic alterations on myocardial function. Moreover, platelets from subjects with diabetes display a typical hyperreactivity explaining the stronger adhesion, activation, and aggregation. Additionally, diabetes provokes an exaggerated stimulation of the endothelium, with an increased release of reactive oxygen species and a reduced release of nitric oxide, both key elements of the endothelial dysfunction. Also, the coagulation cascade and leukocytes activate contributing to this pro-thrombotic environment. Neutrophils have been recently recognized to play a pivotal role by releasing neutrophil extracellular traps. Finally, microparticles from platelets, neutrophils or monocytes are detrimental effectors on the vessel wall and are involved both in vascular dysfunction and in thrombotic complications. Conclusion: In light of these findings, the therapeutic management of diabetes needs to be mostly focused on limiting the progression of complications by targeting precise pathophysiological mechanisms rather than the mere glycemic control, which failed to markedly reduce the risk for macrovascular complications and mortality.

Recent Progress in the Therapeutic Role of Serelaxin in Vascular Dysfunction

2018 ◽  
Vol 19 (11) ◽  
pp. 1079-1087 ◽  
Author(s):  
Ghulam Murtaza ◽  
Adeel Siddiqui ◽  
Izhar Hussain
Keyword(s):  
Recent Progress ◽  
Vascular Dysfunction ◽  
Therapeutic Role

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

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