Biofuel Cell Operating in Vivo in Rat Castorena-Gonzalez, Jorge A.; Foote, Christopher; MacVittie, Kevin ...
Electroanalysis (New York, N.Y.),
July 2013, Volume:
25, Issue:
7
Journal Article
Peer reviewed
Biocatalytic electrodes made of buckypaper were modified with PQQ‐dependent glucose dehydrogenase on the anode and with laccase on the cathode. The enzyme modified electrodes were assembled in a ...biofuel cell which was first characterized in human serum solution and then the electrodes were placed onto exposed rat cremaster tissue. Glucose and oxygen dissolved in blood were used as the fuel and oxidizer, respectively, for the implanted biofuel cell operation. The steady‐state open circuitry voltage of 140±30 mV and short circuitry current of 10±3 µA (current density ca. 5 µA cm−2 based on the geometrical electrode area of 2 cm2) were achieved in the in vivo operating biofuel cell. Future applications of implanted biofuel cells for powering of biomedical and sensor devices are discussed.
We and others have recently reported that prolonged sitting impairs endothelial function in the leg vasculature; however, the mechanism(s) remain unknown. Herein, we tested the hypothesis that a ...sustained reduction in flow-induced shear stress is the underlying mechanism by which sitting induces leg endothelial dysfunction. Specifically, we examined whether preventing the reduction in shear stress during sitting would abolish the detrimental effects of sitting on popliteal artery endothelial function. In 10 young healthy men, bilateral measurements of popliteal artery flow-mediated dilation were performed before and after a 3-h sitting period during which one foot was submerged in 42°C water (i.e., heated) to increase blood flow and thus shear stress, whereas the contralateral leg remained dry and served as internal control (i.e., nonheated). During sitting, popliteal artery mean shear rate was reduced in the nonheated leg (pre-sit, 42.9 ± 4.5 s(-1); and 3-h sit, 23.6 ± 3.3 s(-1); P < 0.05) but not in the heated leg (pre-sit, 38.9 ± 3.4 s(-1); and 3-h sit, 63.9 ± 16.9 s(-1); P > 0.05). Popliteal artery flow-mediated dilation was impaired after 3 h of sitting in the nonheated leg (pre-sit, 7.1 ± 1.4% vs. post-sit, 2.8 ± 0.9%; P < 0.05) but not in the heated leg (pre-sit: 7.3 ± 1.5% vs. post-sit, 10.9 ± 1.8%; P > 0.05). Collectively, these data suggest that preventing the reduction of flow-induced shear stress during prolonged sitting with local heating abolishes the impairment in popliteal artery endothelial function. Thus these findings are consistent with the hypothesis that sitting-induced leg endothelial dysfunction is mediated by a reduction in shear stress.
The Dynamic Structure of Arterioles Martinez-Lemus, Luis A.
Basic & clinical pharmacology & toxicology,
January 2012, Volume:
110, Issue:
1
Journal Article
Peer reviewed
Open access
: Arterioles are the blood vessels in the arterial side of the vascular tree that are located proximal to the capillaries and, in conjunction with the terminal arteries, provide the majority of ...resistance to blood flow. Consequently, arterioles are important contributors to the regulation of mean arterial pressure and tissue perfusion. Their wall consists of cellular and extracellular components that have been traditionally classified as conforming three layers: an intima containing endothelial cells sited on a basement membrane; a media made of an internal elastic lamina apposed by one or two layers of smooth muscle; and an adventitia composed mostly of collagen bundles, nerve endings and some fibroblasts. These components of the arteriolar wall are dynamically interconnected, providing a level of plasticity to the arteriolar wall that blurs the traditional boundaries of a rigid layered classification. This MiniReview focuses on the structural conformation of the arteriolar wall and shows how wall components interact spatially, functionally and temporally to control vascular diameter, regulate blood flow and maintain vascular permeability.
Obesity and cardiovascular disease in women Manrique-Acevedo, Camila; Chinnakotla, Bhavana; Padilla, Jaume ...
International Journal of Obesity,
06/2020, Volume:
44, Issue:
6
Journal Article
Peer reviewed
Open access
As the prevalence of obesity continues to grow worldwide, the health and financial burden of obesity-related comorbidities grows too. Cardiovascular disease (CVD) is clearly associated with increased ...adiposity. Importantly, women are at higher risk of CVD when obese and insulin resistant, in particular at higher risk of developing heart failure with preserved ejection fraction and ischemic heart disease. Increased aldosterone and mineralocorticoid receptor activation, aberrant estrogenic signaling and elevated levels of androgens are among some of the proposed mechanisms explaining the heightened CVD risk. In addition to traditional cardiovascular risk factors, understanding nontraditional risk factors specific to women, like excess weight gain during pregnancy, preeclampsia, gestational diabetes, and menopause are central to designing personalized interventions aimed to curb the epidemic of CVD. In the present review, we examine the available evidence supporting a differential cardiovascular impact of increased adiposity in women compared with men and the proposed pathophysiological mechanisms behind these differences. We also discuss women-specific cardiovascular risk factors associated with obesity and insulin resistance.
Increased sitting time, the most common form of sedentary behavior, is an independent risk factor for all-cause and cardiovascular disease mortality; however, the mechanisms linking sitting to ...cardiovascular risk remain largely elusive. Studies over the last decade have led to the concept that excessive time spent in the sitting position and the ensuing reduction in leg blood flow-induced shear stress cause endothelial dysfunction. This conclusion has been mainly supported by studies using flow-mediated dilation in the lower extremities as the measured outcome. In this review, we summarize evidence from classic studies and more recent ones that collectively support the notion that prolonged sitting-induced leg vascular dysfunction is likely also attributable to changes occurring in vascular smooth muscle cells (VSMCs). Indeed, we provide evidence that prolonged constriction of resistance arteries can lead to modifications in the structural characteristics of the vascular wall, including polymerization of actin filaments in VSMCs and inward remodeling, and that these changes manifest in a time frame that is consistent with the vascular changes observed with prolonged sitting. We expect this review will stimulate future studies with a focus on VSMC cytoskeletal remodeling as a potential target to prevent the detrimental vascular ramifications of too much sitting.
Overnutrition, mTOR signaling, and cardiovascular diseases Jia, Guanghong; Aroor, Annayya R; Martinez-Lemus, Luis A ...
American journal of physiology. Regulatory, integrative and comparative physiology,
11/2014, Volume:
307, Issue:
10
Journal Article
Peer reviewed
Open access
The prevalence of obesity and associated medical disorders has increased dramatically in the United States and throughout much of the world in the past decade. Obesity, induced by excess intake of ...carbohydrates and fats, is a major cause of Type 2 diabetes, hypertension, and the cardiorenal metabolic syndrome. There is emerging evidence that excessive nutrient intake promotes signaling through the mammalian target of rapamycin (mTOR), which, in turn, may lead to alterations of cellular metabolic signaling leading to insulin resistance and obesity-related diseases, such as diabetes, cardiovascular and kidney disease, as well as cancer. While the pivotal role of mTOR signaling in regulating metabolic stress, autophagy, and adaptive immune responses has received increasing attention, there remain many gaps in our knowledge regarding this important nutrient sensor. For example, the precise cellular signaling mechanisms linking excessive nutrient intake and enhanced mTOR signaling with increased cardiovascular and kidney disease, as well as cancer, are not well understood. In this review, we focus on the effects that the interaction between excess intake of nutrients and enhanced mTOR signaling have on the promotion of obesity-associated diseases and potential therapeutic strategies involving targeting mTOR signaling.
Enhanced activation of the mineralocorticoid receptors (MRs) in cardiovascular tissues increases oxidative stress, maladaptive immune responses, and inflammation with associated functional vascular ...abnormalities. We previously demonstrated that consumption of a Western diet (WD) for 16 weeks results in aortic stiffening, and that these abnormalities were prevented by systemic MR blockade in female mice. However, the cell-specific role of endothelial cell MR (ECMR) in these maladaptive vascular effects has not been explored.
We hypothesized that specific deletion of the ECMR would prevent WD-induced increases in endothelial sodium channel activation, reductions in bioavailable nitric oxide, increased vascular remodeling, and associated increases in vascular stiffness in females.
Four-week-old female ECMR knockout and wild-type mice were fed either mouse chow or WD for 16 weeks. WD feeding resulted in aortic stiffness and endothelial dysfunction as determined in vivo by pulse wave velocity and ex vivo by atomic force microscopy, and wire and pressure myography. The WD-induced aortic stiffness was associated with enhanced endothelial sodium channel activation, attenuated endothelial nitric oxide synthase activation, increased oxidative stress, a proinflammatory immune response and fibrosis. Conversely, cell-specific ECMR deficiency prevented WD-induced aortic fibrosis and stiffness in conjunction with reductions in endothelial sodium channel activation, oxidative stress and macrophage proinflammatory polarization, restoration of endothelial nitric oxide synthase activation.
Increased ECMR signaling associated with consumption of a WD plays a key role in endothelial sodium channel activation, reduced nitric oxide production, oxidative stress, and inflammation that lead to aortic remodeling and stiffness in female mice.
Key points
It has been postulated that increased blood flow‐associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin‐stimulated ...vasodilatation.
This report provides evidence supporting the hypothesis that increased shear stress exerts insulin‐sensitizing effects in the vasculature and this evidence is based on experiments in vitro in endothelial cells, ex vivo in isolated arterioles and in vivo in humans.
Given the recognition that vascular insulin signalling, and associated enhanced microvascular perfusion, contributes to glycaemic control and maintenance of vascular health, strategies that stimulate an increase in limb blood flow and shear stress have the potential to have profound metabolic and vascular benefits mediated by improvements in endothelial insulin sensitivity.
The vasodilator actions of insulin contribute to glucose uptake by skeletal muscle, and previous studies have demonstrated that acute and chronic physical activity improves insulin‐stimulated vasodilatation and glucose uptake. Because this effect of exercise primarily manifests in vascular beds highly perfused during exercise, it has been postulated that increased blood flow‐associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin‐stimulated vasodilatation. Accordingly, herein we tested the hypothesis that increased shear stress, in the absence of muscle contraction, can acutely render the vascular endothelium more insulin‐responsive. To test this hypothesis, complementary experiments were conducted using (1) cultured endothelial cells, (2) isolated and pressurized skeletal muscle arterioles from swine, and (3) humans. In cultured endothelial cells, 1 h of increased shear stress from 3 to 20 dynes cm−2 caused a significant shift in insulin signalling characterized by greater activation of eNOS relative to MAPK. Similarly, isolated arterioles exposed to 1 h of intraluminal shear stress (20 dynes cm−2) subsequently exhibited greater insulin‐induced vasodilatation compared to arterioles kept under no‐flow conditions. Finally, we found in humans that increased leg blood flow induced by unilateral limb heating for 1 h subsequently augmented insulin‐stimulated popliteal artery blood flow and muscle perfusion. In aggregate, these findings across models (cells, isolated arterioles and humans) support the hypothesis that elevated shear stress causes the vascular endothelium to become more insulin‐responsive and thus are consistent with the notion that shear stress may be a principal mechanism by which physical activity enhances insulin‐stimulated vasodilatation.
Key points
It has been postulated that increased blood flow‐associated shear stress on endothelial cells is an underlying mechanism by which physical activity enhances insulin‐stimulated vasodilatation.
This report provides evidence supporting the hypothesis that increased shear stress exerts insulin‐sensitizing effects in the vasculature and this evidence is based on experiments in vitro in endothelial cells, ex vivo in isolated arterioles and in vivo in humans.
Given the recognition that vascular insulin signalling, and associated enhanced microvascular perfusion, contributes to glycaemic control and maintenance of vascular health, strategies that stimulate an increase in limb blood flow and shear stress have the potential to have profound metabolic and vascular benefits mediated by improvements in endothelial insulin sensitivity.
The microcirculation is a portion of the vascular circulatory system that consists of resistance arteries, arterioles, capillaries and venules. It is the place where gases and nutrients are exchanged ...between blood and tissues. In addition the microcirculation is the major contributor to blood flow resistance and consequently to regulation of blood pressure. Therefore, structural remodeling of this section of the vascular tree has profound implications on cardiovascular pathophysiology. This review is focused on the role that reactive oxygen species (ROS) play on changing the structural characteristics of vessels within the microcirculation. Particular attention is given to the resistance arteries and the functional pathways that are affected by ROS in these vessels and subsequently induce vascular remodeling. The primary sources of ROS in the microcirculation are identified and the effects of ROS on other microcirculatory remodeling phenomena such as rarefaction and collateralization are briefly reviewed.
Women are especially predisposed to development of arterial stiffening secondary to obesity because of consumption of excessive calories. Enhanced activation of vascular mineralocorticoid receptors ...impairs insulin signaling, induces oxidative stress, inflammation, and maladaptive immune responses. We tested whether a subpressor dose of mineralocorticoid receptor antagonist, spironolactone (1 mg/kg per day) prevents aortic and femoral artery stiffening in female C57BL/6J mice fed a high-fat/high-sugar western diet (WD) for 4 months (ie, from 4-20 weeks of age). Aortic and femoral artery stiffness were assessed using ultrasound, pressurized vessel preparations, and atomic force microscopy. WD induced weight gain and insulin resistance compared with control diet-fed mice and these abnormalities were unaffected by spironolactone. Blood pressures and heart rates were normal and unaffected by diet or spironolactone. Spironolactone prevented WD-induced stiffening of aorta and femoral artery, as well as endothelial and vascular smooth muscle cells, within aortic explants. Spironolactone prevented WD-induced impaired aortic protein kinase B/endothelial nitric oxide synthase signaling, as well as impaired endothelium-dependent and endothelium-independent vasodilation. Spironolactone ameliorated WD-induced aortic medial thickening and fibrosis and the associated activation of the progrowth extracellular receptor kinase 1/2 pathway. Finally, preservation of normal arterial stiffness with spironolactone in WD-fed mice was associated with attenuated systemic and vascular inflammation and an anti-inflammatory shift in vascular immune cell marker genes. Low-dose spironolactone may represent a novel prevention strategy to attenuate vascular inflammation, oxidative stress, and growth pathway signaling and remodeling to prevent development of arterial stiffening secondary to consumption of a WD.
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