The Role of Steroids in Endothelial Function in the Aging Male

2011 ◽  
Vol 07 (02) ◽  
pp. 145
Author(s):  
Antonio Aversa ◽  
Roberto Bruzziches ◽  
Davide Francomano ◽  
Emanuela A Greco ◽  
Silvia Migliaccio ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Major Adverse Cardiovascular Events ◽  
Aging Male ◽  
Vascular Beds ◽  
Endothelial Integrity ◽  
Considerable Body ◽  
Mineralocorticoid Activity ◽  
Circulating Levels

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion, and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during aging and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade, more attention has been drawn to the importance of testosterone, estradiol and adrenal androgens in the pathophysiology, prevention, and treatment of male aging-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and that their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the aging male are frequent and may yield endothelial dysfunction and increased cardiovascular burden. We recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidemia.

The Role of Steroids in Endothelial Function in the Ageing Male

2010 ◽  
Vol 7 (2) ◽  
pp. 115
Author(s):  
Antonio Aversa ◽  
Roberto Bruzziches ◽  
Davide Francomano ◽  
Emanuela A Greco ◽  
Silvia Migliaccio ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Major Adverse Cardiovascular Events ◽  
Ageing Male ◽  
Vascular Beds ◽  
Endothelial Integrity ◽  
Considerable Body ◽  
Mineralocorticoid Activity ◽  
Male Ageing

Normal vascular endothelium is essential for the synthesis and release of substances affecting vascular tone, cell adhesion and the homoeostasis of clotting and fibrinolysis. The degeneration of endothelial integrity promotes adverse events leading to atherogenesis. Circulating levels of endogenous hormones decline during ageing and this may contribute to the occurrence of major adverse cardiovascular events, independently of gender differences. During the last decade more attention has been drawn to the importance of testosterone, oestradiol and adrenal androgens in the pathophysiology, prevention and treatment of male ageing-associated diseases. A considerable body of literature is available indicating that steroid hormones, particularly the sex steroids, are known to modulate endothelial function in all vascular beds and their deficiency may promote endothelial dysfunction. Testosterone decrease and increased mineralocorticoid activity in the ageing male are frequent and may yield endothelial dysfunction and increased cardiovascular burden; we recommend careful hormonal investigations in men who present comorbidities such as diabetes, hypertension and dyslipidaemia.

scholarly journals Abstract 236: Aldehydes in Cigarette Smoke Impair Vascular Endothelial Function

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Poonam Rao ◽  
Pooneh Nabavizadeh Rafsanjani ◽  
Daniel Han ◽  
Suzaynn Schick ◽  
Matthew Springer
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cigarette Smoke ◽  
Secondhand Smoke ◽  
Negative Control ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Gas Generation ◽  
Post Exposure

Introduction: Exposure to tobacco and marijuana smoke impairs vascular endothelial function. While the particulate phase of smoke is heavily implicated, the role of volatile constituents is unclear. Smoke contains aldehydes, which are known to cause endothelial dysfunction. We explored whether two aldehydes found in smoke, acrolein and acetaldehyde, can induce endothelial dysfunction. Hypothesis: Aldehydes in smoke impair endothelial function. Methods: We exposed 4 groups of anesthetized rats to 3 ppm acrolein and 10-11.5 ppm acetaldehyde gases (concentrations relevant to levels in secondhand smoke), Marlboro Red cigarette sidestream smoke at modest levels (600 μg/m 3 PM2.5) as a positive control, and clean air through the gas generation system as a negative control. Exposure was continuous for 10 minutes. Endothelial function (flow-mediated dilation; FMD) was quantified pre- and post-exposure by measuring femoral artery diameter with ultrasound before and after 5 min of transient ischemia and expressed as % vasodilation. Results: Impairment of FMD was observed for acrolein (10.8±1.7(SD)% vs. 5.8±2.9%, p=.001), acetaldehyde (8.8±2.0% vs. 6.0±2.5%, p=.001), and cigarette smoke (9.4±2.9% vs. 5.8±2.0%, p=.002), but not for air (7.9±2.0% vs. 9±3.2%, p=.44) (figure; each colored line denotes a rat pre- and post-exposure; bars denote means). Conclusions: Acrolein and acetaldehyde at levels found in secondhand smoke impair endothelial function. Our results suggest that despite a potential role of particles, volatile aldehydes may mediate part of the endothelial dysfunction caused by exposure to smoke.

scholarly journals Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS?

2019 ◽  
Vol 20 (15) ◽  
pp. 3775 ◽  
Author(s):  
Cesar A. Meza ◽  
Justin D. La Favor ◽  
Do-Houn Kim ◽  
Robert C. Hickner
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Blood Flow ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Vascular Complications ◽  
Enzymatic Production

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

Abstract 3636: The Effects of Arginase II Overexpression on Endothelial Function in Transgenic Mouse Model

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Boris L Vaisman ◽  
Katherine C Wood ◽  
Stephen J Demosky ◽  
Catherine L Knapper ◽  
Jaye Chin-Dusting ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Transgenic Mice ◽  
Endothelial Function ◽  
Transgenic Mouse ◽  
Plasma Lipid ◽  
Aortic Ring ◽  
Normal Function ◽  
Arginase Activity

Endothelium is a major regulator of local vascular homeostasis. Its normal function is crucial for prevention of the development of atherosclerosis, hypertension and other cardiovascular disorders. Reduced nitric oxide (NO) bioavailability is one of the earliest and most important markers of endothelial dysfunction. L-arginine is the substrate for nitric oxide synthases (NOS). Arginase (Arg) can compete with eNOS for L-arginine and thus may play a role in endothelial dysfunction. To further investigate the role of ArgII in endothelial function and in atherosclerosis we generated transgenic mice with human ArgII (hArgII) gene under control of endothelial-specific Tie2 promoter. Expression of hArgII was measured by RT-PCR in eight tissues of transgenic males and compared with the level of mouse ArgII (mArgII) expression in kidneys of normal C57Bl mice, which was taken as 100%. hArgII was expressed at very high levels in all tissues, especially in aorta (2700%), heart (3500%), kidney (1600%), lung (9860%) and muscle (2000%). Arginase activity was elevated 4.6 – 62 fold in all tissues except liver. Lung endothelial cells isolated from hArgII transgenic mice had 4.4-fold greater of arginase activity than whole lung. Resident peritoneal macrophages from hArgII transgenic and normal mice had similar levels of arginase activity, confirming endothelial specificity of the Tie2 promoter. Overexpression of hArgII neither led to significant changes in plasma level of arginine, citrulline, NOHA, ADMA, SDMA and ornithine, nor to changes in plasma lipid levels. However, ArgII overexpression on apoE-knockout background was accompanied by a 10% increase in plasma total cholesterol (p<0.05). hArgII transgenic mice also had blood pressure (mean arterial and diastolic) that averaged 17% higher than controls. Aortic ring segments from hArgII transgenic mice, precontracted with phenylephrine (10 −6 M), exhibited decreased endothelium-dependent relaxation to increasing concentrations of acetylcholine (10 −9 to 10 −3.5 M), indicating endothelial dysfunction secondary to NO insufficiency. These results show that the Tie2hArgII transgenic mouse is a new model for investigating the role of ArgII in endothelial function and in atherosclerosis.

scholarly journals Metabolic disturbances linked to obesity: the role of impaired tissue perfusion

2009 ◽  
Vol 53 (2) ◽  
pp. 238-245 ◽  
Author(s):  
Nivaldo Ribeiro Villela ◽  
Luiz Guilherme Kramer-Aguiar ◽  
Daniel Alexandre Bottino ◽  
Nicolas Wiernsperger ◽  
Eliete Bouskela
Keyword(s):  
Endothelial Dysfunction ◽  
Visceral Obesity ◽  
Microvascular Dysfunction ◽  
Tissue Perfusion ◽  
Early Event ◽  
Internal Diameter ◽  
Metabolic Disturbances ◽  
Vascular Beds ◽  
New Research

Associated with elevated risk of cardiovascular events and cancer, obesity is a worldwide problem affecting developed and developing countries. Microcirculatory vessels, represented by arterioles, capillaries and venules (mean internal diameter < 100 µm), are the place where blood/tissue nutrition and exchange effectively take place. Microvascular dysfunction is an early event in obesity probably secondary to endothelial dysfunction and capillaries rarefaction. New research techniques allow the investigation of the microcirculation in different vascular beds in humans. Studies suggest a link between endothelial dysfunction and visceral obesity. Oxidative stress, inflammation and rennin-angiotensin system are among factors considered to be involved on microvascular dysfunction in obesity. Microcirculatory impairment present in obesity suggests that it could be an important causal factor in obesity-related disorders such as insulin resistance and hypertension.

scholarly journals Caveolin-1 stabilizes ATP7A, a copper transporter for extracellular SOD, in vascular tissue to maintain endothelial function

2020 ◽  
Vol 319 (5) ◽  
pp. C933-C944
Author(s):  
Varadarajan Sudhahar ◽  
Mustafa Nazir Okur ◽  
John P. O’Bryan ◽  
Richard D. Minshall ◽  
David Fulton ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Lipid Rafts ◽  
Vascular Tissue ◽  
Proteasomal Degradation ◽  
Scaffolding Protein ◽  
Copper Transporter ◽  
Caveolin 1

Caveolin-1 (Cav-1) is a scaffolding protein and a major component of caveolae/lipid rafts. Previous reports have shown that endothelial dysfunction in Cav-1-deficient (Cav-1−/−) mice is mediated by elevated oxidative stress through endothelial nitric oxide synthase (eNOS) uncoupling and increased NADPH oxidase. Oxidant stress is the net balance of oxidant generation and scavenging, and the role of Cav-1 as a regulator of antioxidant enzymes in vascular tissue is poorly understood. Extracellular SOD (SOD3) is a copper (Cu)-containing enzyme that is secreted from vascular smooth muscle cells/fibroblasts and subsequently binds to the endothelial cells surface, where it scavenges extracellular [Formula: see text] and preserves endothelial function. SOD3 activity is dependent on Cu, supplied by the Cu transporter ATP7A, but whether Cav-1 regulates the ATP7A-SOD3 axis and its role in oxidative stress-mediated vascular dysfunction has not been studied. Here we show that the activity of SOD3, but not SOD1, was significantly decreased in Cav-1−/− vessels, which was rescued by re-expression of Cav-1 or Cu supplementation. Loss of Cav-1 reduced ATP7A protein, but not mRNA, and this was mediated by ubiquitination of ATP7A and proteasomal degradation. ATP7A bound to Cav-1 and was colocalized with SOD3 in caveolae/lipid rafts or perinucleus in vascular tissues or cells. Impaired endothelium-dependent vasorelaxation in Cav-1−/− mice was rescued by gene transfer of SOD3 or by ATP7A-overexpressing transgenic mice. These data reveal an unexpected role of Cav-1 in stabilizing ATP7A protein expression by preventing its ubiquitination and proteasomal degradation, thereby increasing SOD3 activity, which in turn protects against vascular oxidative stress-mediated endothelial dysfunction.

2229Apoptotic and non-apoptotic circulating microparticles in patients with acute coronary syndromes

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
E Zacharia ◽  
N Papageorgiou ◽  
A S Antonopoulos ◽  
Z Pallantza ◽  
E Oikonomou ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Acute Coronary Syndromes ◽  
Troponin I ◽  
Reactive Protein ◽  
Circulating Microparticles ◽  
Coronary Syndromes ◽  
Stable Cad ◽  
Circulating Levels ◽  
Patient Subgroups

Abstract Background Circulating microparticles (MP) are surrogate biomarkers of atherosclerosis but their role in patients with acute coronary syndromes (ACS) remain unknown. Purpose To explore the levels of apoptotic and non-apoptotic MP in patients with ACS. Methods We enrolled a total of 153 patients as follows: 49 patients with STEMI, 35 NSTEMI, 38 with unstable angina (UA), 15 with stable CAD (SCAD) and 16 non-CAD (controls). Flow cytometry analysis was used to quantify circulating apoptotic (annexin+) and non-apoptotic endothelial cell (EMP), red blood cell (RMP) and platelet (PMP) derived microparticles. Circulating C-reactive protein (hsCRP) levels and cardiac troponin I (cTnI) were also assessed. Brachial FMD was also determined as a marker of endothelial function. Results There was a stepwise increase in the total number of EMP, RMP and PMP in patients with ACS (STEMI/NSTEMI) compared to UA, SCAD and non-CAD patients. This was mainly explained by the increase in the number of apoptotic EMP, RMP and PMP (a-c), while there were no significant differences in the level of apoptotic EMP, RMP or PMP between patient subgroups (not shown). There was no association between circulating levels of apoptotic or non-apoptotic EMP, RBP or PMP with hsCRP (p=NS for all). Apoptotic EMP only were negatively associated with brachial FMD (rho=−0.185, p=0.04) and positively with cTnI levels (rho= 0.307, p<0.0001). Conclusions Circulating apoptotic (but not non-apoptotic) MP are increased in patients with ACS. A negative association is observed between the numbers of circulating apoptotic EMP only and systemic endothelial function. The biological role of circulating apoptotic microparticles' in the pathogenesis of ACS merits further investigation.

scholarly journals ENDOTHELIAL DYSFUNCTION AS PREDICTOR OF SUBCLINICAL AND MANIFEST ATHEROSCLEROSIS

2018 ◽  
Vol 3 (3) ◽  
pp. 39-46
Author(s):  
OV V Fatenkov ◽  
VV V Simerzin ◽  
IV V Gagloeva ◽  
MA A Galkina ◽  
YaA A Panisheva ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Angiotensin Converting Enzyme ◽  
Endothelial Function ◽  
Calcium Antagonists ◽  
Converting Enzyme ◽  
Atherosclerotic Cardiovascular Diseases

This survey presents the role of endothelial dysfunction in pathogenesis of atherosclerotic cardiovascular diseases as predictor of their development. Leading risk factors of endothelial dysfunction and methods of its diagnostics are also shown. Special attention is given to non medicamental correction of endothelial function disorders and its pharmacotherapy with statins, inhibitors of angiotensin converting enzyme (ACE), calcium antagonists and other drugs.

Abstract 080: mTORC1 as a Novel Regulator of Vascular Endothelial Function in Obese Mice and Humans

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
John J Reho ◽  
Deng-Fu Guo ◽  
Andrew Olson ◽  
Lauren Wegman-Points ◽  
Isaac Samuel ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Signaling Pathway ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Obese Mice ◽  
Vascular Endothelial Function ◽  
S6 Kinase ◽  
Mtorc1 Signaling

Obesity-induced hypertension is associated with vascular endothelial dysfunction. Recently, our laboratory has demonstrated a critical role of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in cardiovascular regulation. Here, we tested the hypothesis that dysregulation of mTORC1 signaling is involved in the endothelial dysfunction associated with obesity in mice and humans. We found that diet-induced obese (DIO) mice that display vascular endothelial dysfunction as compared to lean controls have increased mTORC1 signaling in aortic lysates indicated by the elevated (p<0.05) phosphorylated levels of mTOR and its downstream signaling targets S6-kinase and the ribosomal S6 protein measured by Western blot. Increased vascular mTORC1 signaling in DIO mice was associated with increased aortic NOX2 mRNA expression (2.0±0.2 vs. 1.0±0.3AU in lean controls; p<0.05). Isolated abdominal subcutaneous adipose arterioles from non-diabetic obese (BMI ≥30 kg/m 2 ; n=4; age 51±6 yrs; BMI 54±3 kg/m 2 ) humans exhibited a strong trend towards increased phosphorylated S6 protein compared to normal-weight (BMI <30kg/m 2 ; n=3; age 44±15 yrs; BMI 26±1 kg/m 2 ) individuals (5.0±1.9 vs 0.8±0.4AU; p=0.12), suggesting increased vascular mTORC1 signaling in human obesity. Next, we used an adenoviral construct of a constitutively active (CA) S6-kinase (Ad-CAS6K) to enhance mTORC1 signaling. In mouse endothelial cells, Ad-CAS6K increased mRNA expression of oxidative stress (NOX1and NOX2) and inflammatory markers (IL-1β) and decreased endothelial NOS expression (p<0.05). Transfection of aortic rings with the Ad-CAS6K resulted in impairment in acetylcholine-induced relaxation (Max. relaxation: 67± 5 vs. 81 ±3%; p<0.05) without altering the relaxation evoked by sodium nitroprusside (Max. relaxation: 90±1% vs. 90±2%) recapitulating the vascular phenotype in obese mice. Taken together, our data demonstrate a novel role of the mTORC1 signaling pathway in the regulation of vascular endothelial function. Our data also implicate dysregulation of the endothelial mTORC1 signaling pathway in the endothelial dysfunction associated with obesity.

Abstract P314: Effect of Sex on Blood Pressure and Endothelial Dysfunction in the Novel BPH2 Mouse Model of Hypertension

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Sean P Didion
Keyword(s):  
Blood Pressure ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Renin Angiotensin System ◽  
Similar Degree ◽  
The Novel ◽  
Angiotensin System ◽  
Male And Female ◽  
Renin Angiotensin

Very little is known regarding blood pressure and endothelial function between the sexes in the hypertensive BPH2 mouse. Thus, the first goal was determine whether blood pressure and endothelial function are significantly different between male and female BPH2 mice. Information regarding the role of the renin-angiotensin system in the BPH2 mouse is also limited; therefore the second goal was to determine the role of the renin-angiotensin system by treating BPH2 mice with captopril for 4 weeks. Systolic blood pressure (SBP) was significantly elevated (P<0.05) and yet comparable (P>0.05) in male and female BPH2 mice and averaged 140±3 and 136±3 mmHg, respectively, whereas, in control mice SBP averaged 112±4 mmHg. Endothelial responses to acetylcholine in carotid artery were markedly impaired (P<0.05) and to a similar degree in male and female BPH2 mice as compared to controls. Captopril treatment was associated with a significant (P<0.05) reduction in blood pressure of 35±7 and 43±4 mmHg in male and female BPH2 mice, respectively. Captopril also resulted in an improvement of endothelial responses in male and female BPH2 mice. These findings demonstrate that male and female BPH2 mice are equally hypertensive and both sexes are characterized by endothelial dysfunction. In addition, the renin-angiotensin system may contribute to both hypertension and endothelial dysfunction in this model. Taken together, our data define the BPH2 mouse as an important model to compare and contrast the effects of hypertension between the sexes. Supported by NIH HL-107632.

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