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.

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.

scholarly journals The Peroxisome Proliferator-Activated Receptor γ Agonist Pioglitazone Protects Vascular Endothelial Function in Hypercholesterolemic Rats by Inhibiting Myeloperoxidase

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Dapeng Zhang ◽  
Yehong Wang ◽  
Ming Yi ◽  
Suli Zhang ◽  
Ye Wu
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Negative Correlation ◽  
Intervention Group ◽  
Cgmp Level ◽  
Peroxisome Proliferator ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Peroxisome Proliferator Activated Receptor

Objective. Hypercholesterolemia- (HC-) induced endothelial dysfunction is the first step of atherogenesis, and the peroxisome proliferator-activated receptor γ (PPARγ) has been reported to attenuate atherosclerosis formation; however, the underlying mechanisms are not fully understood. The present study was designed to determine whether myeloperoxidase (MPO) mediates HC-induced endothelial dysfunction and the role of the PPARγ agonist pioglitazone (PIO) in attenuating endothelial dysfunction. Methods. Male Wistar rats were fed with normal or high cholesterol diets for 8 weeks. HC rats were randomized to receive dapsone (DDS, the MPO inhibitor) during the last 6 days or PIO for the remaining 4 weeks. Vascular endothelial function was determined by comparing vasorelaxation to ACh, an endothelium-dependent vasodilator, and SNP, an endothelium-independent vasodilator in vascular rings in vitro. The vascular MPO activity, NOx content, and cGMP level were measured by the MPO activity assay kit, NO assay kit, and cGMP RIA kit. Results. Compared with rats fed with normal diet, endothelium-dependent vasodilation, NOx content, and cGMP level were decreased, and MPO activity was increased in thoracic aortas of rats fed with HC diet. There was a negative correlation between vascular endothelial function, NOx content or cGMP level, and MPO activity. PIO obviously reduced the MPO activity, increased NOx content and cGMP level, and improved endothelium-dependent vasodilation function in HC rats, which was essentially the same as that seen with DDS. And, there was a negative correlation between vascular endothelial function, NOx content or cGMP level, and MPO activity in the HC group and the PIO intervention group. Conclusion. MPO might provoke vascular endothelial dysfunction in hypercholesterolemic rats by reducing the NO biological activity and impairing the NO/cGMP/cGK signaling pathway. PIO might inhibit vascular MPO activity and increase NO bioavailability with the net result of reversing endothelial dysfunction.

Abstract 344: Kruppel-like Factor 15: A Critical Transcriptional Regulator of Hypoxia Induced Endothelial Arginase 2

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Deepesh Pandey ◽  
Dan Berkowitz ◽  
Lew Romer
Keyword(s):  
Endothelial Function ◽  
Chromatin Immunoprecipitation ◽  
Pulmonary Arteries ◽  
Microvascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Protein Levels ◽  
Direct Binding ◽  
Novel Therapeutic Strategies

Objective: Kruppel Like Factor 15 has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that a KLF15 is a critical regulator of Arg2 transcription in response to hypoxia. Approach and Results: Adenoviral mediated augmented expression of KLF15 in human pulmonary microvascular endothelial cells (HPMEC) and in rat pulmonary arteries decreased Arg2 mRNA, protein, and activity. HPMECs exposed to 48 hours of hypoxia exhibited a robust increase in Arg2 protein and mRNA expression and a reciprocal decrease in KLF15 protein levels that remain sustained after 24 hours of reoxygenation. Further, decreased KLF15 protein levels observed in hypoxia exposed HPMEC occurs through augmented conjugation of Ubiquitin to KLF15 that results in enhanced clearance of KLF15 via proteasomal degradation. Chromatin immunoprecipitation indicated direct binding of KLF15 to the Arg2 promoter, which was relieved when HPMEC were exposed to hypoxia, Finally, overexpression of KLF15 reversed hypoxia-induced augmentation of arginase activity and decrements in Nitric Oxide production in HPMEC, and also reversed hypoxia-induced endothelial dysfunction in isolated mice aortic and rat pulmonary artery rings. Conclusions: KLF15 is a critical regulator and repressor of endothelial Arg2 expression, and thereby, NO and pulmonary endothelial function. Overexpression or activation of KLF15 may represent novel therapeutic strategies for pulmonary hypertension.

scholarly journals Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function

2017 ◽  
Vol 313 (5) ◽  
pp. H890-H895 ◽  
Author(s):  
Matthew J. Rossman ◽  
Rachelle E. Kaplon ◽  
Sierra D. Hill ◽  
Molly N. McNamara ◽  
Jessica R. Santos-Parker ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cell Senescence ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Healthy Humans ◽  
Age Related ◽  
Habitual Exercise

Cellular senescence is emerging as a key mechanism of age-related vascular endothelial dysfunction, but evidence in healthy humans is lacking. Moreover, the influence of lifestyle factors such as habitual exercise on endothelial cell (EC) senescence is unknown. We tested the hypothesis that EC senescence increases with sedentary, but not physically active, aging and is associated with vascular endothelial dysfunction. Protein expression (quantitative immunofluorescence) of p53, a transcription factor related to increased cellular senescence, and the cyclin-dependent kinase inhibitors p21 and p16 were 116%, 119%, and 128% greater (all P < 0.05), respectively, in ECs obtained from antecubital veins of older sedentary (60 ± 1 yr, n = 12) versus young sedentary (22 ± 1 yr, n = 9) adults. These age-related differences were not present (all P > 0.05) in venous ECs from older exercising adults (57 ± 1 yr, n = 13). Furthermore, venous EC protein levels of p53 ( r = −0.49, P = 0.003), p21 ( r = −0.38, P = 0.03), and p16 ( r = −0.58, P = 0.002) were inversely associated with vascular endothelial function (brachial artery flow-mediated dilation). Similarly, protein expression of p53 and p21 was 26% and 23% higher (both P < 0.05), respectively, in ECs sampled from brachial arteries of healthy older sedentary (63 ± 1 yr, n = 18) versus young sedentary (25 ± 1 yr, n = 9) adults; age-related changes in arterial EC p53 and p21 expression were not observed ( P > 0.05) in older habitually exercising adults (59 ± 1 yr, n = 14). These data indicate that EC senescence is associated with sedentary aging and is linked to endothelial dysfunction. Moreover, these data suggest that prevention of EC senescence may be one mechanism by which aerobic exercise protects against endothelial dysfunction with age. NEW & NOTEWORTHY Our study provides novel evidence in humans of increased endothelial cell senescence with sedentary aging, which is associated with impaired vascular endothelial function. Furthermore, our data suggest an absence of age-related increases in endothelial cell senescence in older exercising adults, which is linked with preserved vascular endothelial function. Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-exercise-and-endothelial-cell-senescence/ .

scholarly journals Improvement in Vascular Endothelial Function following Transcatheter Aortic Valve Implantation

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1008
Author(s):  
Shuhei Tanaka ◽  
Teruhiko Imamura ◽  
Ryuichi Ushijima ◽  
Mitsuo Sobajima ◽  
Nobuyuki Fukuda ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Aortic Valve ◽  
Aortic Stenosis ◽  
Endothelial Function ◽  
Severe Aortic Stenosis ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Transcatheter Aortic Valve ◽  
Aortic Valve Implantation ◽  
Valve Implantation

Background and objectives: Endothelial dysfunction is associated with exercise intolerance and adverse cardiovascular events. Transcatheter aortic valve implantation (TAVI) is applied to treat elderly patients with severe aortic stenosis, but less is known about the impact of TAVI on endothelial dysfunction, which can be assessed by measuring flow-mediated vasodilation (FMD). In this parameter, a low value indicates impaired endothelial function. Materials and Methods: Vascular endothelial function was evaluated by FMD of the brachial artery just before and one week after TAVI. Factors associated with the normalization of FMD and their prognostic impact were investigated. Results: Fifty-one patients who underwent TAVI procedure (median 86 years old, 12 men) were included. FMD improved significantly from baseline to one week following TAVI (from 5.3% [3.7%, 6.7%] to 6.3% [4.7%, 8.1%], p < 0.001). Among 33 patients with baseline low FMD (≤6.0%), FMD normalized up to >6.0% following TAVI in 15 patients. Baseline higher cardiac index was independently associated with normalization of FMD following TAVI (odds ratio 11.8, 95% confidence interval 1.12–124; p < 0.04). Conclusions: Endothelial dysfunction improved following TAVI in many patients with severe aortic stenosis. The implication of this finding is the next concern.

Abstract 041: Elevated Circulating Copeptin in Mid-Gestation is Associated with Increased Aortic Stiffness and Vascular Endothelial Dysfunction in Pregnant Women at High Risk for Preeclampsia

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Gary L Pierce ◽  
Donna A Santillan ◽  
Diedre Fleener ◽  
Sabrina M Scroggins ◽  
Kimberlly K Leslie ◽  
...  
Keyword(s):  
High Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Pregnant Women ◽  
Brachial Artery ◽  
Aortic Stiffness ◽  
Vascular Dysfunction ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function

Circulating copeptin, a stable biomarker of vasopressin (AVP) secretion, is elevated throughout pregnancy in women who develop preeclampsia (PreE) and is a strong predictor of PreE as early as the 6th week gestation. Reduced vascular endothelial function and increased aortic stiffness occur in mid-gestation before clinical signs/symptoms of PreE manifest, suggesting that maternal vascular dysfunction may be an early event in the pathogenesis of PreE. However, it is unknown whether elevated copeptin/AVP in early/mid gestation contributes to vascular dysfunction in pregnant women who subsequently develop PreE. Therefore, we hypothesized that elevated copeptin would be associated with increased aortic stiffness and reduced vascular endothelial function in early/mid gestation of pregnant women at high risk for PreE. Pregnant women in the 1st trimester (n=72; age=30 ±1 yrs; BMI=34 ± 1 kg/m2) with at least 1 risk factor for PreE were enrolled. Aortic stiffness (carotid-femoral pulse wave velocity, CFPWV), vascular endothelial function (brachial artery flow-mediated dilation, FMD), blood pressure (BP) and plasma copeptin (ELISA) were assessed in both the 1st (11.7 ± 0.2 wks) and 2nd (18.8 ± 0.4 wks) trimesters. In the 1st trimester, CFPWV (7.3 ± 0.2 vs. 7.3 ± 0.5 m/sec, P=0.86), brachial artery FMD (12.9 ± 1.1 vs. 14.3 ± 2.0%, P=0.53), BP, BMI and age did not differ between women in the highest (1513 ± 221 pg/ml) vs. lowest (279 ± 12 pg/ml) quartile of copeptin (P<0.01). In contrast, 2nd trimester CFPWV was greater (7.2 ± 0.2 vs. 6.4 ± 0.2 m/sec, P<0.05) and brachial artery FMD was lower (10.2 ± 2.8 vs. 16.5 ± 1.3 %, P<0.05) among women in the highest (1714 ± 481 pg/ml) vs. the lowest (249 ± 13 pg/ml) quartile of copeptin (P<0.01), in the absence of differences in BP, BMI or age. For the entire cohort, (log)copeptin was significantly correlated with CFPWV (r=0.23, P=0.04) and tended to correlate with FMD (r=-0.23, P=0.06) in the 2nd but not in the 1st trimester. These data suggest that elevated copeptin in mid-gestation is associated with aortic stiffness and vascular endothelial dysfunction in pregnant women at high risk for PreE, but whether increased copeptin/AVP causes vascular dysfunction in pregnancies destined for PreE requires further studies using animal models.

scholarly journals Endothelial Dysfunction in Cystic Fibrosis: Role of Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Matthew A. Tucker ◽  
Brandon M. Fox ◽  
Nichole Seigler ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cystic Fibrosis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Dysfunction ◽  
Lipid Hydroperoxide ◽  
Vascular Endothelial ◽  
Vascular Endothelial Dysfunction ◽  
Vascular Endothelial Function ◽  
Artery Flow

Oxidative stress and vascular endothelial dysfunction are established characteristics of cystic fibrosis (CF). Oxidative stress may contribute to vascular dysfunction via inhibition of nitric oxide (NO) bioavailability. Purpose. To determine if ingestion of a single antioxidant cocktail (AOC) improves vascular endothelial function in patients with CF. Methods. In 18 patients with CF (age 8-39 y), brachial artery flow-mediated dilation (FMD) was assessed using a Doppler ultrasound prior to and two hours following either an AOC (n=18; 1,000 mg vitamin C, 600 IU vitamin E, and 600 mg α-lipoic acid) or a placebo (n=9). In a subgroup of patients (n=9), changes in serum concentrations of α-tocopherol and lipid hydroperoxide (LOOH) were assessed following AOC and placebo. Results. A significant (p=0.032) increase in FMD was observed following AOC (Δ1.9±3.3%), compared to no change following placebo (Δ−0.8±1.9%). Moreover, compared with placebo, AOC prevented the decrease in α-tocopherol (Δ0.48±2.91 vs. −1.98±2.32 μM, p=0.024) and tended to decrease LOOH (Δ−0.2±0.1 vs. 0.1±0.1 μM, p=0.063). Conclusions. These data demonstrate that ingestion of an antioxidant cocktail can improve vascular endothelial function and improve oxidative stress in patients with CF, providing evidence that oxidative stress is a key contributor to vascular endothelial dysfunction in CF.

Aerobic exercise offsets endothelial dysfunction induced by repetitive consumption of sugar-sweetened beverages in young healthy men

2020 ◽  
Vol 319 (1) ◽  
pp. R11-R18
Author(s):  
Joshua M. Bock ◽  
Erika Iwamoto ◽  
Jeffrey G. Horak ◽  
Andrew J. Feider ◽  
Satoshi Hanada ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Aerobic Exercise ◽  
Fasting Glucose ◽  
Area Under The Curve ◽  
Moderate Intensity ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Sugar Sweetened Beverage ◽  
Beneficial Effects

Consumption of a single, sugar-sweetened beverage (SSB) impairs vascular endothelial function. Regular aerobic exercise improves endothelium-dependent vasodilation; however, it is unknown whether these beneficial effects persist with frequent SSB consumption. Therefore, the purpose of this study was twofold; we studied the effects of repetitive SSB consumption (75 g d-glucose, 3 times/day) for 1 wk (Glu, n = 13, 23 ± 4 yr, 23.5 ± 3.4 kg/m2) on endothelium-dependent vasodilation (FMD). Then, in a separate cohort, we investigated whether 45 min of moderate-intensity aerobic exercise on five separate days offset the hypothesized decrease in FMD during the Glu protocol (Glu+Ex, n = 11, 21 ± 3 yr, 23.8 ± 2.4 kg/m2). Baseline, fasting [glucose] ( P = 0.15), [insulin] ( P = 0.25), %FMD ( P = 0.48), absolute FMD ( P = 0.66), and shear rate area under the curve (SRAUC; P = 0.82) were similar between groups. Following the interventions, fasting [glucose] (Glu: 94 ± 6 to 92 ± 6 mg/dL, Glu+Ex: 89 ± 8 to 87 ± 6 mg/dL, P = 0.74) and [insulin] (Glu: 11.3 ± 6.2 to 11.8 ± 8.9 μU/mL, Glu+Ex: 8.7 ± 2.9 to 9.4 ± 3.2 μU/mL, P = 0.89) were unchanged. %FMD was reduced in Glu (6.1 ± 2.2 to 5.1 ± 1.3%) and increased in Glu+Ex (6.6 ± 2.2 to 7.8 ± 2.4%, P < 0.05 for both). SRAUC increased similarly in both Glu [17,715 ± 8,275 to 22,922 ± 4,808 arbitrary units (A.U.)] and Glu+Ex (18,216 ± 4,516 to 21,666 ± 5,392 A.U., main effect of time P < 0.05). When %FMD was adjusted for SRAUC, attenuation was observed in Glu (0.41 ± 0.18 to 0.23 ± 0.08%/s × 103, P < 0.05) but not Glu+Ex (0.38 ± 0.14 to 0.38 ± 0.13%/s × 103, P = 0.88). Despite unchanged fasting [glucose] and [insulin], repeated consumption of SSBs impaired conduit artery vascular endothelial function. Additionally, subjects who engaged in regular moderate-intensity aerobic exercise did not demonstrate the same SSB-induced endothelial dysfunction. Collectively, these data suggest aerobic exercise may offset the deleterious effects of repetitive SSB consumption.

Sign in / Sign up

Export Citation Format

Share Document