Publications by authors named "Kayla Branyan"

9 Publications

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Chronic stress induced perivascular adipose tissue impairment of aortic function and the therapeutic effect of exercise.

Exp Physiol 2021 Apr 28. Epub 2021 Apr 28.

Department of Exercise Physiology.

New Findings: What is the central question of this study? tPVAT is known to, in part, regulate aortic function. However, the role of tPVAT in aortic impairment associated with chronic exposure to psychosocial stressors (Unpredictable Chronic Mild Stress; UCMS) is unknown. Thus, the purpose of this study is to examine the effects of UCMS on the tPVAT regulation of aortic function. Secondly, we wanted to determine the role of exercise training on alleviating the potential negative actions of UCMS on tPVAT. What is the main finding and its importance? The main finding of this study is that UCMS causes tPVAT to disrupt endothelial dependent dilation. UCMS increased inflammatory cytokine production and diminished tPVAT-adiponectin. Exercise training proved efficacious in preventing tPVAT-mediated disruption of aortic function. Together, our data support a tPVAT-mechanism through which chronic stress negatively impacts vascular health and adds to our knowledge of how psychological disorders might increase the risk of cardiovascular disease.

Abstract: Chronic stress is a major risk for cardiovascular disease. Perivascular adipose tissue (PVAT) has been shown to regulate vascular function, however, the impact of chronic stress and the comorbidity of metabolic syndrome (MetS) on thoracic (t)PVAT are unknown. Additionally, aerobic exercise training (AET) is known to combat the pathology of MetS and chronic stress, but the role of tPVAT in these actions are also unknown. Therefore, the purpose of this study is to examine the effects of unpredictable chronic mild stress (UCMS) on the tPVAT regulation of aortic function and the preventative effect of AET. Methods & Results Lean (LZR) and obese (OZR) Zucker rats (16-17-week-old) were exposed to 8 weeks of UCMS with and without treadmill exercise (AET). In LZR, UCMS impaired aortic endothelial-dependent dilation (EDD) (assessed ex-vivo by wire-myography), and aortic stiffness (assessed by elastic modulus) with no change in OZR UCMS. However, both LZR and OZR UCMS tPVAT impaired EDD compared to respective controls. LZR and OZR UCMS had higher oxidative stress production, diminished adiponectin, and impaired aortic nitric oxide levels. Divergently, UCMS induced greater inflammatory cytokine production in LZR UCMS tPVAT, but not in OZR UCMS tPVAT. AET prevented the tPVAT impairment of aortic relaxation with UCMS in LZR and OZR. Additionally, AET reduced aortic stiffness in both LZR and OZR. These beneficial effects on tPVAT regulation of the aorta are likely due to AET preservation of adiponectin, reduced oxidative stress and inflammation, and enhanced nitric oxide. Conclusion UCMS impaired tPVAT-regulated aortic function in LZR, and augmented MetS-induced EDD in OZR. Conversely, AET in combination with UCMS largely preserved aortic function and the tPVAT environment, in both groups. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1113/EP089449DOI Listing
April 2021

Exercise training prevents the perivascular adipose tissue-induced aortic dysfunction with metabolic syndrome.

Redox Biol 2019 09 26;26:101285. Epub 2019 Jul 26.

Division of Exercise Physiology, WVU School of Medicine, Morgantown, WV, USA; Department of Neuroscience, WVU School of Medicine, Morgantown, WV, USA. Electronic address:

The aim of the study was to determine the effects of exercise training on improving the thoracic perivascular adipose tissue (tPVAT) phenotype (inflammation, oxidative stress, and proteasome function) in metabolic syndrome and its subsequent actions on aortic function.

Methods: Lean and obese (model of metabolic syndrome) Zucker rats (n=8/group) underwent 8-weeks of control conditions or treadmill exercise (70% of max speed, 1 h/day, 5 days/week). At the end of the intervention, the tPVAT was removed and conditioned media was made. The cleaned aorta was attached to a force transducer to assess endothelium-dependent and independent dilation in the presence or absence of tPVAT-conditioned media. tPVAT gene expression, inflammatory /oxidative phenotype, and proteasome function were assessed.

Results: The main findings were that Ex induced: (1) a beige-like, anti-inflammatory tPVAT phenotype; (2) a greater abundance of NO in tPVAT; (3) a reduction in tPVAT oxidant production; and (4) an improved tPVAT proteasome function. Regarding aortic function, endothelium-dependent dilation was greater in exercised lean and obese groups vs. controls (p < 0.05). Lean control tPVAT improved aortic relaxation, whereas obese control tPVAT decreased aortic relaxation. In contrast, the obese Ex-tPVAT increased aortic dilation, whereas the lean Ex-tPVAT did not affect aortic dilation.

Conclusion: Overall, exercise had the most dramatic impact on the obese tPVAT reflecting a change towards an environment with less oxidant load, less inflammation and improved proteasome function. Such beneficial changes to the tPVAT micro-environment with exercise likely played a significant role in mediating the improvement in aortic function in metabolic syndrome following 8 weeks of exercise.
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http://dx.doi.org/10.1016/j.redox.2019.101285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669320PMC
September 2019

Psychological stress-induced cerebrovascular dysfunction: the role of metabolic syndrome and exercise.

Exp Physiol 2018 05 25;103(5):761-776. Epub 2018 Mar 25.

Division of Exercise Physiology, West Virginia University Health Sciences Center, Morgantown, WV, USA.

New Findings: What is the central question of this study? How does chronic stress impact cerebrovascular function and does metabolic syndrome accelerate the cerebrovascular adaptations to stress? What role does exercise training have in preventing cerebrovascular changes to stress and metabolic syndrome? What is the main finding and its importance? Stressful conditions lead to pathological adaptations of the cerebrovasculature via an oxidative nitric oxide pathway, and the presence of metabolic syndrome produces a greater susceptibility to stress-induced cerebrovascular dysfunction. The results also provide insight into the mechanisms that may contribute to the influence of stress and the role of exercise in preventing the negative actions of stress on cerebrovascular function and structure.

Abstract: Chronic unresolvable stress leads to the development of depression and cardiovascular disease. There is a high prevalence of depression with the metabolic syndrome (MetS), but to what extent the MetS concurrent with psychological stress affects cerebrovascular function is unknown. We investigated the differential effect of MetS on cerebrovascular structure/function in rats (16-17 weeks old) following 8 weeks of unpredictable chronic mild stress (UCMS) and whether exercise training could limit any cerebrovascular dysfunction. In healthy lean Zucker rats (LZR), UCMS decreased (28%, P < 0.05) ex vivo middle cerebral artery (MCA) endothelium-dependent dilatation (EDD), but changes in MCA remodelling and stiffness were not evident, though cerebral microvessel density (MVD) decreased (30%, P < 0.05). The presence of UCMS and MetS (obese Zucker rats; OZR) decreased MCA EDD (35%, P < 0.05) and dilatation to sodium nitroprusside (20%, P < 0.05), while MCA stiffness increased and cerebral MVD decreased (31%, P < 0.05), which were linked to reduced nitric oxide and increased oxidative levels. Aerobic exercise prevented UCMS impairments in MCA function and MVD in LZR, and partly restored MCA function, stiffness and MVD in OZR. Our data suggest that the benefits of exercise with UCMS were due to a reduction in oxidative stress and increased production of nitric oxide in the cerebral vessels. In conclusion, UCMS significantly impaired MCA structure and function, but the effects of UCMS were more substantial in OZR vs. LZR. Importantly, aerobic exercise when combined with UCMS prevented the MCA dysfunction through subtle shifts in nitric oxide and oxidative stress in the cerebral microvasculature.
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http://dx.doi.org/10.1113/EP086892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927836PMC
May 2018

Aortic dysfunction in metabolic syndrome mediated by perivascular adipose tissue TNFα- and NOX2-dependent pathway.

Exp Physiol 2018 04 28;103(4):590-603. Epub 2018 Feb 28.

Division of Exercise Physiology, West Virginia University School of Medicine, Morgantown, WV, USA.

New Findings: What is the central question of this study? Tumour necrosis factor-α (TNFα) has been shown to impair vascular function, but the impact of thoracic aorta perivascular adipose tissue (tPVAT)-derived TNFα on tPVAT and aortic function in metabolic syndrome is unknown. What is the main finding and its importance? Release of TNFα by tPVAT causes production of reactive oxygen species in tPVAT through activation of an NADPH-oxidase 2 (NOX2)-dependent pathway, activates production of aortic reactive oxygen species and mediates aortic stiffness, potentially through matrix metalloproteinase 9 activity. Neutralization of TNFα and/or inhibition of NOX2 blocks the tPVAT-induced impairment of aortic function. These data partly implicate tPVAT NOX2 and TNFα in mediating the vascular pathology of metabolic syndrome.

Abstract: Perivascular adipose tissue (PVAT) is recognized for its vasoactive effects, but it is unclear how metabolic syndrome impacts thoracic aorta (t)PVAT and the subsequent effect on functional and structural aortic stiffness. Thoracic aorta and tPVAT were removed from 16- to 17-week-old lean (LZR, n = 16) and obese Zucker rats (OZR, n = 16). The OZR presented with aortic endothelial dysfunction, assessed by wire myography, and increased aortic stiffness, assessed by elastic modulus. The OZR tPVAT exudate further exacerbated the endothelial dysfunction, reducing nitric oxide and endothelium-dependent relaxation (P < 0.05). Additionally, OZR tPVAT exudate had increased MMP9 activity (P < 0.05) and further increased the elastic modulus of the aorta after 72 h of co-culture (P < 0.05). We found that the observed aortic dysfunction caused by OZR tPVAT was mediated through increased production and release of tumour necrosis factor-α (TNFα; P < 0.01), which was dependent on tPVAT NADPH-oxidase 2 (NOX2) activity. The OZR tPVAT release of reactive oxygen species and subsequent aortic dysfunction were inhibited by TNFα neutralization and/or inhibition of NOX2. Additionally, we found that OZR tPVAT had reduced activity of the active sites of the 20S proteasome (P < 0.05) and reduced superoxide dismutase activity (P < 0.01). In conclusion, metabolic syndrome causes tPVAT dysfunction through an interplay between TNFα and NOX2 that leads to tPVAT-mediated aortic stiffness by activation of aortic reactive oxygen species and increased MMP9 activity.
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http://dx.doi.org/10.1113/EP086818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5878714PMC
April 2018

Role of Chronic Stress and Exercise on Microvascular Function in Metabolic Syndrome.

Med Sci Sports Exerc 2018 05;50(5):957-966

Division of Exercise Physiology, School of Medicine, West Virginia University, Morgantown, WV.

Purpose: The present study examined the effect of unpredictable chronic mild stress (UCMS) on peripheral microvessel function in healthy and metabolic syndrome (MetS) rodents and whether exercise training could prevent the vascular dysfunction associated with UCMS.

Methods: Lean and obese (model of MetS) Zucker rats (LZR and OZR) were exposed to 8 wk of UCMS, exercise (Ex), UCMS + Ex, or control conditions. At the end of the intervention, gracilis arterioles (GA) were isolated and hung in a pressurized myobath to assess endothelium-dependent (EDD) and endothelium-independent (EID) dilation. Levels of nitric oxide (NO) and reactive oxygen species (ROS) were measured through 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate and dihydroethidium staining, respectively.

Results: Compared with LZR controls, EDD and EID were lower (P = 0.0001) in LZR-UCMS. The OZR-Ex group had a higher EDD (P = 0.0001) and EID (P = 0.003) compared with OZR controls, whereas only a difference in EDD (P = 0.01) was noted between the LZR-control and LZR-Ex groups. Importantly, EDD and EID were higher in the LZR (P = 0.0001; P = 0.02) and OZR (P = 0.0001; P = 0.02) UCMS + Ex groups compared with UCMS alone. Lower NO bioavailability and higher ROS were noted in the LZR-UCMS group (P = 0.0001), but not OZR-UCMS, compared with controls. The Ex and UCMS-Ex groups had higher NO bioavailability (P = 0.0001) compared with the control and UCMS groups, but ROS levels remained high.

Conclusions: The comorbidity between UCMS and MetS does not exacerbate the effects of one another on GA EDD responses, but does lead to the development of other vasculopathy adaptations, which can be partially explained by alterations in NO and ROS production. Importantly, exercise training alleviates most of the negative effects of UCMS on GA function.
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http://dx.doi.org/10.1249/MSS.0000000000001531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5898979PMC
May 2018

Chronic exposure to electronic cigarettes results in impaired cardiovascular function in mice.

J Appl Physiol (1985) 2018 03 2;124(3):573-582. Epub 2017 Nov 2.

Division of Exercise Physiology, School of Medicine, West Virginia University , Morgantown, West Virginia.

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.
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http://dx.doi.org/10.1152/japplphysiol.00713.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899271PMC
March 2018

Circulating leucocytes perpetuate stroke-induced aortic dysfunction.

Exp Physiol 2017 10 2;102(10):1321-1331. Epub 2017 Sep 2.

Division of Exercise Physiology, West Virginia University, Morgantown, WV, USA.

New Findings: What is the central question of this study? Does a stroke event influence aortic endothelial function; and what is the role of peripheral circulating leucocytes in stroke on the vascular reactivity of the aorta? What is the main finding and its importance? In vitro co-culture experiments demonstrated that aortic endothelium-dependent relaxation was impaired when rat aortic rings were co-cultured with leucocytes stimulated with serum from stroke patients. Impaired vascular reactivity was not observed in aortic rings without leucocytes stimulated with serum from stroke patients or age-matched control patients with or without leucocytes. These data suggest that leucocyte-dependent altered aortic endothelium-dependent relaxation with stroke and the systemic consequences of stroke on vascular inflammation may occur in the aorta. Post-stroke inflammation has been linked to poor stroke outcomes. The vascular endothelium senses and responds to circulating factors, in particular inflammatory cytokines. Although stroke-associated local cerebrovascular dysfunction is well reported, the effects of a stroke on conduit artery function are not fully understood. We tested the hypothesis that serum from stroke patients triggers leucocyte-dependent aortic endothelial dysfunction that is associated with elevated concentrations of cytokines. Total leucocytes were isolated from healthy individuals, and the cells were incubated in serum from control subjects or stroke patients for 6 h. The quantity of cytokines in media was determined using an immunoassay. Vascular reactivity was determined by the rat aortic rings that were co-cultured with or without leucocytes and stimulated with serum samples from control subjects or stroke patients. Endothelium-dependent dilatation was significantly impaired in aortic rings co-cultured with leucocytes plus serum from stroke patients (50 ± 30 versus 85 ± 13%, P < 0.05) versus serum from control subjects. In contrast, no difference was observed in aortic function stimulated with serum from control subjects or stroke patients without total leucocytes. Likewise, total leucocyte-derived cytokine concentrations were significantly increased in a time-dependent manner on stimulation with serum from stroke patients (P < 0.05). These observations support the concept that the increased response of leucocytes drives the development of stroke-associated vascular endothelial dysfunction. As such, pharmacologically targeting the source of inflammatory cytokines might alleviate stroke-associated peripheral vascular dysfunction.
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http://dx.doi.org/10.1113/EP086510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5623140PMC
October 2017

Cerebral Cortical Microvascular Rarefaction in Metabolic Syndrome is Dependent on Insulin Resistance and Loss of Nitric Oxide Bioavailability.

Microcirculation 2015 Aug;22(6):435-45

Clinical and Translational Sciences Institute, West Virginia University Health Sciences Center, Morgantown, West Virginia, USA.

Objective: Chronic presentation of the MS is associated with an increased likelihood for stroke and poor stroke outcomes following occlusive cerebrovascular events. However, the physiological mechanisms contributing to compromised outcomes remain unclear, and the degree of cerebral cortical MVD may represent a central determinant of stroke outcomes.

Methods: This study used the OZR model of MS and clinically relevant, chronic interventions to determine the impact on cerebral cortical microvascular rarefaction via immunohistochemistry with a parallel determination of cerebrovascular function to identify putative mechanistic contributors.

Results: OZR exhibited a progressive rarefaction (to ~80% control MVD) of the cortical microvascular networks vs. lean Zucker rats. Chronic treatment with antihypertensive agents (captopril/hydralazine) had limited effectiveness in blunting rarefaction, although treatments improving glycemic control (metformin/rosiglitazone) were superior, maintaining ~94% control MVD. Chronic treatment with the antioxidant TEMPOL severely blunted rarefaction in OZR, although this ameliorative effect was prevented by concurrent NOS inhibition.

Conclusions: Further analyses revealed that the maintenance of glycemic control and vascular NO bioavailability were stronger predictors of cerebral cortical MVD in OZR than was prevention of hypertension, and this may have implications for chronic treatment of CVD risk under stroke-prone conditions.
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http://dx.doi.org/10.1111/micc.12209DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551443PMC
August 2015

Late-emigrating trunk neural crest cells in turtle embryos generate an osteogenic ectomesenchyme in the plastron.

Dev Dyn 2013 Nov 6;242(11):1223-35. Epub 2013 Sep 6.

Biology Department, Millersville University, Millersville, Pennsylvania.

Background: The turtle plastron is composed of a keratinized epidermis overlying nine dermal bones. Its developmental origin has been controversial; recent evidence suggests that the plastral bones derive from trunk neural crest cells (NCCs).

Results: This study extends the observations that there is a turtle-specific, second wave of trunk NCC delamination and migration, after the original NCCs have reached their destination and differentiated. This second wave was confirmed by immunohistochemistry in whole-mounts and serial sections, by injecting DiI (1,1', di-octadecyl-3,3,3',3',-tetramethylindo-carbocyanine perchlorate) into the lumen of the neural tube and tracing labeled cells into the plastron, and by isolating neural tubes from older turtle embryos and observing delaminating NCCs. This later migration gives rise to a plastral ectomesenchyme that expresses NCC markers and can be induced to initiate bone formation.

Conclusions: The NCCs of this second migration have properties similar to those of the earlier NCCs, but also express markers characteristic of cranial NCCs. The majority of the cells of the plastron mesenchyme express neural crest markers, and have osteogenic differentiation capabilities that are similar or identical to craniofacial ectomesenchyme. Our evidence supports the contention that turtle plastron bones are derived from a late emigrating population of cells derived from the trunk neural crest.
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http://dx.doi.org/10.1002/dvdy.24018DOI Listing
November 2013