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Plastics and cardiovascular health: phthalates may disrupt heart rate variability and cardiovascular reactivity
This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices. NEW & NOTEWORTHY Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Jaimes, R., Swiercz, A., Sherman, M., Muselimyan, N., Marvar, P. J., Posnack, N. G. Tags: RESEARCH ARTICLE Source Type: research

Effect of ovariectomy on intracellular Ca2+ regulation in guinea pig cardiomyocytes
This study addressed the hypothesis that long-term deficiency of ovarian hormones after ovariectomy (OVx) alters cellular Ca2+-handling mechanisms in the heart, resulting in the formation of a proarrhythmic substrate. It also tested whether estrogen supplementation to OVx animals reverses any alterations to cardiac Ca2+ handling and rescues proarrhythmic behavior. OVx or sham operations were performed on female guinea pigs using appropriate anesthetic and analgesic regimes. Pellets containing 17β-estradiol (1 mg, 60-day release) were placed subcutaneously in selected OVx animals (OVx + E). Cardiac myocytes were enzyma...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Yang, H.-Y., Firth, J. M., Francis, A. J., Alvarez-Laviada, A., MacLeod, K. T. Tags: RESEARCH ARTICLE Source Type: research

Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening
In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA. NEW & NOTEWORTHY Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify tar...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Polonis, K., Somers, V. K., Becari, C., Covassin, N., Schulte, P. J., Druliner, B. R., Johnson, R. A., Narkiewicz, K., Boardman, L. A., Singh, P. Tags: RESEARCH ARTICLE Source Type: research

An update on hormone therapy in postmenopausal women: mini-review for the basic scientist
The worlds of observational, clinical, and basic science collided in 2002 with the publication of results of the Women’s Health Initiative (WHI), a large-scale, prospective, blinded, randomized-controlled trial designed to provide evidence regarding use of hormone treatment to prevent cardiovascular disease in menopausal women. The results of the WHI dramatically changed clinical practice, negatively impacted funding for hormone research, and left scientists to unravel the "why" of the results. Now over a decade and a half since the initial publication of the WHI results, basic and clinical scientists often do not in...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Miller, V. M., Harman, S. M. Tags: REVIEW Source Type: research

Role of pattern recognition receptors of the neurovascular unit in inflamm-aging
Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge abou...
Source: AJP: Heart and Circulatory Physiology - November 6, 2017 Category: Cardiology Authors: Wilhelm, I., Nyul-Toth, A., Kozma, M., Farkas, A. E., Krizbai, I. A. Tags: REVIEW Source Type: research

Preconditioning with the BKCa channel activator NS-1619 prevents ischemia-reperfusion-induced inflammation and mucosal barrier dysfunction: roles for ROS and heme oxygenase-1
Activation of large-conductance Ca2+-activated K+ (BKCa) channels evokes cell survival programs that mitigate intestinal ischemia and reperfusion (I/R) inflammation and injury 24 h later. The goal of the present study was to determine the roles of reactive oxygen species (ROS) and heme oxygenase (HO)-1 in delayed acquisition of tolerance to I/R induced by pretreatment with the BKCa channel opener NS-1619. Superior mesentery arteries were occluded for 45 min followed by reperfusion for 70 min in wild-type (WT) or HO-1-null (HO-1–/–) mice that were pretreated with NS-1619 or saline vehicle 24 h earlier. Intravita...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Dai, H., Wang, M., Patel, P. N., Kalogeris, T., Liu, Y., Durante, W., Korthuis, R. J. Tags: RESEARCH ARTICLE Source Type: research

Primed polymorphonuclear leukocytes from hemodialysis patients enhance monocyte transendothelial migration
Increased counts and priming of peripheral polymorphonuclear leukocytes (PMNLs) are associated with future or ongoing atherosclerosis; however, the role of PMNLs in enhancing monocyte transendothelial migration is still unclear. Our aims were to examine endothelial and monocyte activation, transmigration, and posttransmigration activation induced ex vivo by in vivo primed PMNLs and the effect of antioxidants on the activation. A unique ex vivo coculture system of three cell types was developed in this study, enabling interactions among the following: primary human umbilical vein endothelial cells (HUVECs), monocytes (THP-1...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Kliger, E., Kristal, B., Shapiro, G., Chezar, J., Sela, S. Tags: RESEARCH ARTICLE Source Type: research

Visualization of three pathways for macromolecule transport across cultured endothelium and their modification by flow
Transport of macromolecules across vascular endothelium and its modification by fluid mechanical forces are important for normal tissue function and in the development of atherosclerosis. However, the routes by which macromolecules cross endothelium, the hemodynamic stresses that maintain endothelial physiology or trigger disease, and the dependence of transendothelial transport on hemodynamic stresses are controversial. We visualized pathways for macromolecule transport and determined the effect on these pathways of different types of flow. Endothelial monolayers were cultured under static conditions or on an orbital shak...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Ghim, M., Alpresa, P., Yang, S.-W., Braakman, S. T., Gray, S. G., Sherwin, S. J., van Reeuwijk, M., Weinberg, P. D. Tags: RESEARCH ARTICLE Source Type: research

Shock and lethality with anthrax edema toxin in rats are associated with reduced arterial responsiveness to phenylephrine and are reversed with adefovir
In conclusion, in rats, hypotension and lethality are associated with reduced arterial contractile function with ETx but not LTx and adefovir improves ETx-induced hypotension and lethality. NEW & NOTEWORTHY The most important aspects of the present study are the findings that 1) in vivo challenge with anthrax edema but not lethal toxin depresses arterial contractile function measured both ex vivo and in vivo and 2) adefovir inhibits the effects of edema toxin on arterial hypotension and improves survival with lethal dose of edema toxin challenge. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Suffredini, D. A., Li, Y., Xu, W., Moayeri, M., Leppla, S., Fitz, Y., Cui, X., Eichacker, P. Q. Tags: RESEARCH ARTICLE Source Type: research

Inhibitory actions of the NRG-1/ErbB4 pathway in macrophages during tissue fibrosis in the heart, skin, and lung
In this study, we hypothesized that the antifibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages. We also hypothesized that the antifibrotic effect of NRG-1 may be active in other organs, such as the skin and lung. First, in a mouse model of angiotensin II (ANG II)-induced myocardial hypertrophy and fibrosis, NRG-1 treatment (20 µg·kg–1·day–1 ip) significantly attenuated myocardial hypertrophy and fibrosis and improved passive ventricular stiffness (4 wk). Interestingly, 1 wk after exposure to ANG II, NRG-1 already attenuated myocardi...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Vermeulen, Z., Hervent, A.-S., Dugaucquier, L., Vandekerckhove, L., Rombouts, M., Beyens, M., Schrijvers, D. M., De Meyer, G. R. Y., Maudsley, S., De Keulenaer, G. W., Segers, V. F. M. Tags: RESEARCH ARTICLE Source Type: research

Mineralocorticoids: the secret of muscle reflex dysfunction in hypertension?
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Wang, H.-J. Tags: EDITORIAL FOCUS Source Type: research

How does pressure overload cause cardiac hypertrophy and dysfunction? High-ouabain affinity cardiac Na+ pumps are crucial
Left ventricular hypertrophy is frequently observed in hypertensive patients and is believed to be due to the pressure overload and cardiomyocyte stretch. Three recent reports on mice with genetically engineered Na+ pumps, however, have demonstrated that cardiac ouabain-sensitive α2-Na+ pumps play a key role in the pathogenesis of transaortic constriction-induced hypertrophy. Hypertrophy was delayed/attenuated in mice with mutant, ouabain-resistant α2-Na+ pumps and in mice with cardiac-selective knockout or transgenic overexpression of α2-Na+ pumps. The latter, seemingly paradoxical, findings can be expla...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Blaustein, M. P. Tags: REVIEW Source Type: research

Dietary modulation of oxylipins in cardiovascular disease and aging
Oxylipins are a group of fatty acid metabolites generated via oxygenation of polyunsaturated fatty acids and are involved in processes such as inflammation, immunity, pain, vascular tone, and coagulation. As a result, oxylipins have been implicated in many conditions characterized by these processes, including cardiovascular disease and aging. The best characterized oxylipins in relation to cardiovascular disease are derived from the -6 fatty acid arachidonic acid. These oxylipins generally increase inflammation, hypertension, and platelet aggregation, although not universally. Similarly, oxylipins derived from the -6 fatt...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Caligiuri, S. P. B., Parikh, M., Stamenkovic, A., Pierce, G. N., Aukema, H. M. Tags: REVIEW Source Type: research

Vascular niche contribution to age-associated neural stem cell dysfunction
Neural stem cells (NSCs) persist throughout life in the dentate gyrus and the ventricular-subventricular zone, where they continuously provide new neurons and some glia. These cells are found in specialized niches that regulate quiescence, activation, differentiation, and cell fate choice. A key aspect of the regulatory niche is the vascular plexus, which modulates NSC behavior during tissue homeostasis and regeneration. During aging, NSCs become depleted and dysfunctional, resulting in reduced neurogenesis and poor brain repair. In this review, we discuss the emerging evidence that changes in the vascular niche both struc...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Apple, D. M., Kokovay, E. Tags: REVIEW Source Type: research

Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function
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% g...
Source: AJP: Heart and Circulatory Physiology - November 1, 2017 Category: Cardiology Authors: Rossman, M. J., Kaplon, R. E., Hill, S. D., McNamara, M. N., Santos-Parker, J. R., Pierce, G. L., Seals, D. R., Donato, A. J. Tags: RAPID REPORT Source Type: research