scholarly journals Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice

2018 ◽  
Vol 124 (3) ◽  
pp. 573-582 ◽  
Author(s):  
I. Mark Olfert ◽  
Evan DeVallance ◽  
Hannah Hoskinson ◽  
Kayla W. Branyan ◽  
Stuart Clayton ◽  
...  
Keyword(s):  
Arterial Stiffness ◽  
Cardiac Function ◽  
Vascular Function ◽  
Chronic Exposure ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Electronic Cigarettes ◽  
Whole Body ◽  
Daily Exposure

Proponents for electronic cigarettes (E-cigs) claim that they are a safe alternative to tobacco-based cigarettes; however, little is known about the long-term effects of exposure to E-cig vapor on vascular function. The purpose of this study was to determine the cardiovascular consequences of chronic E-cig exposure. Female mice (C57BL/6 background strain) were randomly assigned to chronic daily exposure to E-cig vapor, standard (3R4F reference) cigarette smoke, or filtered air ( n = 15/group). Respective whole body exposures consisted of four 1-h-exposure time blocks, separated by 30-min intervals of fresh air breaks, resulting in intermittent daily exposure for a total of 4 h/day, 5 days/wk for 8 mo. Noninvasive ultrasonography was used to assess cardiac function and aortic arterial stiffness (AS), measured as pulse wave velocity, at three times points (before, during, and after chronic exposure). Upon completion of the 8-mo exposure, ex vivo wire tension myography and force transduction were used to measure changes in thoracic aortic tension in response to vasoactive-inducing compounds. AS increased 2.5- and 2.8-fold in E-cig- and 3R4F-exposed mice, respectively, compared with air-exposed control mice ( P < 0.05). The maximal aortic relaxation to methacholine was 24% and 33% lower in E-cig- and 3R4F-exposed mice, respectively, than in controls ( P < 0.05). No differences were noted in sodium nitroprusside dilation between the groups. 3R4F exposure altered cardiac function by reducing fractional shortening and ejection fraction after 8 mo ( P < 0.05). A similar, although not statistically significant, tendency was also observed with E-cig exposure ( P < 0.10). Histological and respiratory function data support emphysema-associated changes in 3R4F-exposed, but not E-cig-exposed, mice. Chronic exposure to E-cig vapor accelerates AS, significantly impairs aortic endothelial function, and may lead to impaired cardiac function. The clinical implication from this study is that chronic use of E-cigs, even at relatively low exposure levels, induces cardiovascular dysfunction. NEW & NOTEWORTHY Electronic cigarettes (E-cigs) are marketed as safe, but there has been insufficient long-term exposure to humans to justify these claims. This is the first study to report the long-term in vivo vascular consequences of 8 mo of exposure to E-cig vapor in mice (equivalent to ~25 yr of exposure in humans). We report that E-cig exposure increases arterial stiffness and impairs normal vascular reactivity responses, similar to other risk factors, including cigarette smoking, which contribute to the development of cardiovascular disease.

Homocyst(e)ine impairs endocardial endothelial function

1999 ◽  
Vol 77 (12) ◽  
pp. 950-957 ◽  
Author(s):  
Suresh C Tyagi ◽  
Lane M Smiley ◽  
Vibhas S Mujumdar
Keyword(s):  
Nitric Oxide ◽  
Methyl Ester ◽  
Cardiac Function ◽  
Vascular Function ◽  
Ex Vivo ◽  
Cardiac Contraction ◽  
Normal Male ◽  
Wistar Kyoto ◽  
Endocardial Endothelium ◽  
Endothelial Nitric Oxide

Homocyst(e)ine injured vascular endothelium and modulated endothelial-dependent vascular function. Endothelium plays an analogous role in both the vessel and the endocardium. Therefore, we hypothesized that homocyst(e)ine modulated endocardial endothelium (EE) dependent cardiac function. The ex vivo cardiac rings from normal male Wistar-Kyoto rats were prepared. The contractile responses of left and right ventricular rings were measured in an isometric myobath, using different concentrations of CaCl2. The response was higher in the left ventricle than right ventricle and was elevated in endocardium without endothelium. The half effective concentration (EC50) and maximum tension generated by homocyst(e)ine were 106 and 5-fold lower than endothelin (ET) and angiotensin II (AII), respectively. However, in endothelial-denuded endocardium, homocyst(e)ine response was significantly increased (p < 0.005, compared with intact endothelium) and equal to the response to ET and AII. To determine the physiological significance of ET, AII, homocyst(e)ine, and endothelial nitric oxide in EE function, cardiac rings were pretreated with AII (10-10 M) or ET (10-13 M) and then treated with homocyst(e)ine (10-8 M). Results suggested that at these concentrations AII, ET, or homocyst(e)ine alone had no effect on cardiac contraction. However, in the presence of 10-10 M AII or 10-13 M ET, the cardiac contraction to homocyst(e)ine (10-8 M) was significantly enhanced (p < 0.01, compared with without pretreatment) and further increased in the endocardium without endothelium. The pretreatment of cardiac ring with the inhibitor of nitric oxide, Nω-nitro-L-arginine methyl ester (L-NAME), increased contractile response to homocyst(e)ine. These results suggested that homocyst(e)ine impaired EE-dependent cardiac function and acted synergistically with AII and ET in enhancing the cardiac contraction.Key words: endocardial remodeling, homocyst(e)ine, contraction, endothelin, angiotensin, endothelial-derived relaxing factor (EDRF), Nω-nitro-L-arginine methyl ester (L-NAME), endothelial dysfunction, ex vivo cardiac function, heart failure.

Improvements in vascular function in response to acute lower limb heating in young healthy males and females

2021 ◽  
Author(s):  
Jem L. Cheng ◽  
Jennifer S. Williams ◽  
Sven Hoekstra ◽  
Maureen J. MacDonald
Keyword(s):  
Arterial Stiffness ◽  
Endothelial Function ◽  
Upper Limb ◽  
Lower Limb ◽  
Vascular Function ◽  
Water Immersion ◽  
Plasma Concentrations ◽  
Hot Water ◽  
Whole Body ◽  
Vascular Conductance

Regular exposure to passive heat stress improves vascular function, but the optimal heating prescription remains undefined. Local limb heating is more feasible than whole body heating, but the evidence demonstrating its efficacy is lacking. The purpose of this study was to determine whether acute improvements in vascular function can be achieved with lower limb heating in 16 young healthy individuals (8 female, 8 male). In separate visits, participants underwent 45-min of ankle- and knee-level hot water immersion (45 °C). A subset of 7 participants also participated in a time-control visit. Endothelial function was assessed through simultaneous brachial and superficial femoral artery flow-mediated dilation (FMD) tests. Macrovascular function was quantified by %FMD, while microvascular function was quantified by vascular conductance during reactive hyperemia. Arterial stiffness was assessed through carotid-femoral and femoral-foot pulse wave velocity (PWV). Plasma concentrations of interleukin-6 and extracellular heat shock protein-72 (eHSP72) were used as indicators of inflammation. Our findings showed that 45-min of lower limb heating - regardless of condition - acutely improved upper limb macrovascular endothelial function (i.e., brachial %FMD; Pre: 4.6±1.7 vs. Post: 5.4±2.0%; P=0.004) and lower limb arterial stiffness (i.e., femoral-foot PWV; Pre: 8.4±1.2 vs. Post: 7.7±1.1 m/s; P=0.011). However, only knee-level heating increased upper limb microvascular endothelial function (i.e., brachial peak vascular conductance; Pre: 6.3±2.7 vs. Post: 7.8±3.5 ml/min⋅mmHg; P≤0.050) and plasma eHSP72 concentration (Pre: 12.4±9.4 vs. Post: 14.8±9.8 ng/ml; P≤0.050). These findings show that local lower limb heating acutely improves vascular function in younger individuals, with knee-level heating improving more outcome measures.

Role of whey protein in vascular function: a systematic review and meta-analysis of human intervention studies

2021 ◽  
pp. 1-34
Author(s):  
Fatemeh Hajizadeh-Sharafabad ◽  
Elham Sharifi Zahabi ◽  
Ali Tarighat-Esfanjani
Keyword(s):  
Systematic Review ◽  
Arterial Stiffness ◽  
Whey Protein ◽  
Vascular Function ◽  
English Language ◽  
Vascular Reactivity ◽  
Augmentation Index ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Effect Sizes

Abstract Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarizing the effects of WP consumption on vascular reactivity, arterial stiffness, and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS, and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, 16 were included in our systematic review and 13 in meta-analysis. The pooled analysis of 6 studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (WMD: 1.09%, 95% CI: 0.17, 2.01, P=0.01). Meta-analysis of available data didn’t show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: −0.29%, 95% CI: −1.58, 0.98, P=0.64) and pulse wave velocity (effect sizes: 4, WMD: −0.72 m/s, 95% CI: −1.47, 0.03, P=0.06). Moreover, the pooled analysis of 6 effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0.42 μmol/L, 95% CI: −0.52 to 1.36, P=0.38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

Abstract P285: Aging In Male Mice Is Characterized By Arterial Stiffening And Diastolic Dysfunction

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Benard O Ogola ◽  
Bruna Visniauskas ◽  
Isabella Kilanowski-doroh ◽  
Caleb M Abshire ◽  
Alec Horton ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Arterial Stiffness ◽  
Cardiac Function ◽  
Vascular Function ◽  
Posterior Wall ◽  
Left Ventricular ◽  
Male Mice ◽  
Middle Aged ◽  
Mature Adult ◽  
Arterial Stiffening

Aging is a nonmodifiable risk factor for cardiovascular mortality and is associated with arterial stiffening and cardiac dysfunction. In this study, we hypothesized that aging would decrease vascular compliance and cardiac function in male mice. Tail-cuff plethysmography was used to measure blood pressure, pulse wave velocity (PWV) for arterial stiffness, echocardiography for systolic and diastolic cardiac function, and wire myography for vessel reactivity in mature adult (25 weeks) and middle-aged (57 weeks) C57Bl/6 mice. Data was analyzed by t-test or 2-way ANOVA, and P<0.05 was considered significant. While there was no difference in blood pressure, PWV was higher in middle-aged male mice (1.8 ± 0.04 m/s vs. 1.2 ± 0.05 m/s; P<0.001) and associated with increased left ventricular (LV) posterior wall thickness (1.4 ± 0.07 mm vs. 1.1 ± 0.13 mm; P=0.03), and LV mass (172 ± 8 mg vs. 158 ± 20 mg; P=0.04). The ratio of early to late filling velocities, a measure of diastolic function, was lower in middle-age (1.6 ± 0.07 vs. 2.7 ± 0.37; P<0.001). Carotid artery histological analysis indicated that middle-aged mice had a greater collagen-to-elastin ratio along with decreased amounts of smooth muscle and thin collagen (P<0.05). Mesenteric artery contraction to PGF2α (446 ± 15% vs. 378 ± 14%; P=0.02) as well as relaxation to sodium nitroprusside (55 ± 7% vs. 31 ± 7%; P<0.01) were both blunted in the middle-aged group. The current study demonstrates that aging in male mice increases arterial stiffening and LV remodeling while decreasing diastolic and vascular function, independent of increased blood pressure. Future studies will investigate whether strategies that counteract arterial stiffness in the absence of changes in blood pressure can protect from cardiovascular aging.

scholarly journals Measuring Arterial Stiffness in Animal Experimental Studies

2020 ◽  
Vol 40 (5) ◽  
pp. 1068-1077
Author(s):  
Mark Butlin ◽  
Isabella Tan ◽  
Bart Spronck ◽  
Alberto P. Avolio
Keyword(s):  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Animal Studies ◽  
Ex Vivo ◽  
Experimental Studies ◽  
Full Characterization ◽  
Invasive Techniques

The arterial wall is a composite material of elastin, collagen, and extracellular matrix with acutely modifiable material properties through the action of smooth muscle cells. Therefore, arterial stiffness is a complex parameter that changes not only with long-term remodeling of the wall constituents but also with acute contraction or relaxation of smooth muscle or with changes in the acute distending pressure to which the artery is exposed. It is not possible to test all these aspects using noninvasive or even invasive techniques in humans. Full characterization of the mechanical properties of the artery and the specific arterial factors causing changes to stiffness with disease or modified lifestyle currently require animal studies. This article summarizes the major in vivo and ex vivo techniques to measure the different aspects of arterial stiffness in animal studies.

scholarly journals A dual apolipoprotein C-II mimetic–apolipoprotein C-III antagonist peptide lowers plasma triglycerides

2020 ◽  
Vol 12 (528) ◽  
pp. eaaw7905 ◽  
Author(s):  
Anna Wolska ◽  
Larry Lo ◽  
Denis O. Sviridov ◽  
Mohsen Pourmousa ◽  
Milton Pryor ◽  
...  
Keyword(s):  
Nonhuman Primates ◽  
Ex Vivo ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Dynamics Simulation ◽  
Whole Body ◽  
High Density Lipoproteins ◽  
Apolipoprotein C

Recent genetic studies have established that hypertriglyceridemia (HTG) is causally related to cardiovascular disease, making it an active area for drug development. We describe a strategy for lowering triglycerides (TGs) with an apolipoprotein C-II (apoC-II) mimetic peptide called D6PV that activates lipoprotein lipase (LPL), the main plasma TG-hydrolyzing enzyme, and antagonizes the TG-raising effect of apoC-III. The design of D6PV was motivated by a combination of all-atom molecular dynamics simulation of apoC-II on the Anton 2 supercomputer, structural prediction programs, and biophysical techniques. Efficacy of D6PV was assessed ex vivo in human HTG plasma and was found to be more potent than full-length apoC-II in activating LPL. D6PV markedly lowered TG by more than 80% within a few hours in both apoC-II–deficient mice and hAPOC3-transgenic (Tg) mice. In hAPOC3-Tg mice, D6PV treatment reduced plasma apoC-III by 80% and apoB by 65%. Furthermore, low-density lipoprotein (LDL) cholesterol did not accumulate but rather was decreased by 10% when hAPOC3-Tg mice lacking the LDL-receptor (hAPOC3-Tg × Ldlr−/−) were treated with the peptide. D6PV lowered TG by 50% in whole-body inducible Lpl knockout (iLpl−/−) mice, confirming that it can also act independently of LPL. D6PV displayed good subcutaneous bioavailability of about 80% in nonhuman primates. Because it binds to high-density lipoproteins, which serve as a long-term reservoir, it also has an extended terminal half-life (42 to 50 hours) in nonhuman primates. In summary, D6PV decreases plasma TG by acting as a dual apoC-II mimetic and apoC-III antagonist, thereby demonstrating its potential as a treatment for HTG.

scholarly journals Evaluation of the Acute Effects of Traditional Persian Medicine Based Hot and Cold Foods on Metabolic Responses and Arterial Stiffness in Healthy Men: Study Protocol for a Randomized Controlled Trial

2020 ◽  
Author(s):  
Mohsen Zakerian ◽  
Fatemeh Roudi ◽  
Reza Rezvani ◽  
Malihe Motavasselian
Keyword(s):  
Arterial Stiffness ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Controlled Trial ◽  
Main Tool ◽  
Metabolic Responses ◽  
Normal Body Mass Index ◽  
Healthy Men ◽  
Persian Medicine ◽  
Traditional Persian Medicine

Abstract Background: Traditional Persian Medicine (TPM)-based temperament is affected by some determinant factors that seems to have close similarities to resting energy expenditure (REE) and thermic effect of food (TEF) determinants. Pulse characteristics is considered as a main tool distinguishing different temperaments and vascular function and the probability of cardiovascular events are different in hot and cold-temper individuals in TPM point of view. Additionally, all foods are divided into cold/hot-temper and dry/wet-temper in this medical school and may lead to different responses in subjects regarding their temperaments.Methods: This experiment will be an acute phase study that will be performed on two groups of healthy individuals with normal body mass index (BMI) with hot and cold temperament. Each person will receive two TPM-based hot/cold isocaloric breakfast meals in 2 different days and metabolic responses and arterial stiffness indices thorough blood samples, indirect calorimetry, and pulse wave analysis and velocimetry will be assessed at fasting state, 0.5, 2, and 4 hours following meal consumption. Discussion: We will investigate the metabolic differences between individuals with TPM-based hot and cold temperaments and also to evaluate the effects of different TPM-based temperament of isocaloric meals (hot and cold) on metabolic responses and arterial stiffness indices in TPM-based hot/cold temper healthy men in this study. The results of this research project may lead to design of novel combined TPM and modern nutrition-based diet planning to improve metabolic responses and vascular reactivity. Trial registration: International Clinical Trials Registry Platform IRCT20200417047105N1, retrospectively registered at 19/04/2020. URL: https://irct.ir/trial/47267.

scholarly journals The SWELL1-LRRC8 complex regulates endothelial AKT-eNOS-mTOR signaling and vascular function

2020 ◽  
Author(s):  
Ahmad F. Alghanem ◽  
Chau Ta ◽  
Joshua M. Maurer ◽  
Susheel K. Gunasekar ◽  
Ashutosh Kumar ◽  
...  
Keyword(s):  
Blood Flow ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Umbilical Vein ◽  
Anion Channel ◽  
Aortic Ring ◽  
Tube Formation ◽  
Mtor Signaling ◽  
Retinal Blood Flow

AbstractThe endothelium responds to a multitude of chemical and mechanical factors in regulating vascular tone, angiogenesis, blood pressure and blood flow. The endothelial volume regulatory anion channel (VRAC) has been proposed to be mechano-sensitive, to activate in response to fluid flow/hydrostatic pressure and putatively regulate vascular reactivity and angiogenesis. Here, we show that the Leucine Rich Repeat Containing Protein 8a, LRRC8a (SWELL1) functionally encodes VRAC in human umbilical vein endothelial cells (HUVECs). Endothelial SWELL1 (SWELL1) expression positively regulates AKT-eNOS signaling while negatively regulating mTOR signaling, via a SWELL1-GRB2-Cav1-eNOS signaling complex. Endothelium-restricted SWELL1 KO (SWELL1 KO) mice exhibit enhanced tube formation from ex-vivo aortic ring explants in matrigel angiogenesis assays, develop hypertension in response to chronic angiotensin II infusion and have impaired retinal blood flow with both diffuse and focal blood vessel narrowing in the setting of Type 2 diabetes (T2D). These data demonstrate that SWELL1 antithetically regulates AKT-eNOS and mTOR signaling in endothelium and is required for maintaining vascular function, particularly in the setting of T2D.

scholarly journals Doxorubicin Impairs Smooth Muscle Cell Contraction: Novel Insights in Vascular Toxicity

2021 ◽  
Vol 22 (23) ◽  
pp. 12812
Author(s):  
Matthias Bosman ◽  
Dustin N. Krüger ◽  
Kasper Favere ◽  
Callan D. Wesley ◽  
Cédric H. G. Neutel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Arterial Stiffness ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Reactivity ◽  
Transient Receptor Potential ◽  
Ex Vivo ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels

Clinical and animal studies have demonstrated that chemotherapeutic doxorubicin (DOX) increases arterial stiffness, a predictor of cardiovascular risk. Despite consensus about DOX-impaired endothelium-dependent vasodilation as a contributing mechanism, some studies have reported conflicting results on vascular smooth muscle cell (VSMC) function after DOX treatment. The present study aimed to investigate the effects of DOX on VSMC function. To this end, mice received a single injection of 4 mg DOX/kg, or mouse aortic segments were treated ex vivo with 1 μM DOX, followed by vascular reactivity evaluation 16 h later. Phenylephrine (PE)-induced VSMC contraction was decreased after DOX treatment. DOX did not affect the transient PE contraction dependent on Ca2+ release from the sarcoplasmic reticulum (0 mM Ca2+), but it reduced the subsequent tonic phase characterised by Ca2+ influx. These findings were supported by similar angiotensin II and attenuated endothelin-1 contractions. The involvement of voltage-gated Ca2+ channels in DOX-decreased contraction was excluded by using levcromakalim and diltiazem in PE-induced contraction and corroborated by similar K+ and serotonin contractions. Despite the evaluation of multiple blockers of transient receptor potential channels, the exact mechanism for DOX-decreased VSMC contraction remains elusive. Surprisingly, DOX reduced ex vivo but not in vivo arterial stiffness, highlighting the importance of appropriate timing for evaluating arterial stiffness in DOX-treated patients.

Methylene blue alleviates endothelial dysfunction and reduces oxidative stress in aortas from diabetic rats

2018 ◽  
Vol 96 (10) ◽  
pp. 1012-1016 ◽  
Author(s):  
Andreea I. Privistirescu ◽  
Alexandra Sima ◽  
Oana M. Duicu ◽  
Romulus Timar ◽  
Mariana G. Roșca ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Methylene Blue ◽  
Endothelial Dysfunction ◽  
Vascular Function ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Xylenol Orange ◽  
Diabetic Rat ◽  
Ros Production ◽  
Protective Effects

Endothelial dysfunction and the related increase in reactive oxygen species (ROS) production are important events in the pathophysiology of diabetes mellitus (DM). Methylene blue (MB) has been systematically investigated for its protective effects against refractory hypotension and mitochondrial dysfunction. We have previously demonstrated that MB improved mitochondrial respiration and partially decreased oxidative stress in diabetic rat hearts. The present study was aimed to investigate whether MB modulates vascular function and ROS production in thoracic aortic rings isolated from rats with streptozotocin-induced DM (after 4 weeks of hyperglycemia). The effects of MB (0.1 μM, 30 min ex vivo incubation) on vascular reactivity in organ chamber (phenylephrine-induced contraction, acetylcholine-induced relaxation) and H2O2production (assessed by ferrous iron xylenol orange oxidation assay) were investigated in vascular preparations with intact endothelium and after denudation. DM elicited a significant alteration of vascular function: increased contractility to phenylephrine, attenuation of acetylcholine-dependent relaxation, and augmented H2O2generation. Ex vivo incubation with MB partially reversed all these changes (by approximately 70%) in vascular segments with intact endothelial layer (but not in denuded vessels). In conclusion, MB might be useful in alleviating endothelial dysfunction and mitigating endothelial oxidative stress, observations that clearly require further investigation in the setting of cardiometabolic disease.

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