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Acute exposure to progesterone attenuates cardiac contraction by modifying myofilament calcium sensitivity in the female mouse heart
Acute application of progesterone attenuates cardiac contraction, although the underlying mechanisms are unclear. We investigated whether progesterone modified contraction in isolated ventricular myocytes and identified the Ca2+ handling mechanisms involved in female C57BL/6 mice (6–9 mo; sodium pentobarbital anesthesia). Cells were field-stimulated (4 Hz; 37°C) and exposed to progesterone (0.001–10.0 μM) or vehicle (35 min). Ca2+ transients (fura-2) and cell shortening were recorded simultaneously. Maximal concentrations of progesterone inhibited peak contraction by 71.4% (IC50 = 160 ± 50 nM; n =...
Source: AJP: Heart and Circulatory Physiology - December 31, 2016 Category: Cardiology Authors: Feridooni, H. A., MacDonald, J. K., Ghimire, A., Pyle, W. G., Howlett, S. E. Tags: RESEARCH ARTICLE Source Type: research

Role of microRNA in metabolic shift during heart failure
Heart failure (HF) is an end point resulting from a number of disease states. The prognosis for HF patients is poor with survival rates precipitously low. Energy metabolism is centrally linked to the development of HF, and it involves the proteomic remodeling of numerous pathways, many of which are targeted to the mitochondrion. microRNAs (miRNA) are noncoding RNAs that influence posttranscriptional gene regulation. miRNA have garnered considerable attention for their ability to orchestrate changes to the transcriptome, and ultimately the proteome, during HF. Recently, interest in the role played by miRNA in the regulation...
Source: AJP: Heart and Circulatory Physiology - December 31, 2016 Category: Cardiology Authors: Pinti, M. V., Hathaway, Q. A., Hollander, J. M. Tags: REVIEW Source Type: research

Decoding the vasoregulatory activities of bile acid-activated receptors in systemic and portal circulation: role of gaseous mediators
Bile acids are end products of cholesterol metabolism generated in the liver and released in the intestine. Primary and secondary bile acids are the result of the symbiotic relation between the host and intestinal microbiota. In addition to their role in nutrient absorption, bile acids are increasingly recognized as regulatory signals that exert their function beyond the intestine by activating a network of membrane and nuclear receptors. The best characterized of these bile acid-activated receptors, GPBAR1 (also known as TGR5) and the farnesosid-X-receptor (FXR), have also been detected in the vascular system and their ac...
Source: AJP: Heart and Circulatory Physiology - December 31, 2016 Category: Cardiology Authors: Fiorucci, S., Zampella, A., Cirino, G., Bucci, M., Distrutti, E. Tags: REVIEW Source Type: research

Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging
Increasing evidence from epidemiological, clinical and experimental studies indicate that age-related cerebromicrovascular dysfunction and microcirculatory damage play critical roles in the pathogenesis of many types of dementia in the elderly, including Alzheimer’s disease. Understanding and targeting the age-related pathophysiological mechanisms that underlie vascular contributions to cognitive impairment and dementia (VCID) are expected to have a major role in preserving brain health in older individuals. Maintenance of cerebral perfusion, protecting the microcirculation from high pressure-induced damage and momen...
Source: AJP: Heart and Circulatory Physiology - December 31, 2016 Category: Cardiology Authors: Toth, P., Tarantini, S., Csiszar, A., Ungvari, Z. Tags: REVIEW Source Type: research

Corrigendum
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Tags: CORRIGENDA Source Type: research

Microstructure and mechanics of human resistance arteries
We present a new methodology for stain-free visualization, at a microscopic scale, of the morphology of the main passive components of the walls of unfixed resistance arteries and their response to changes in transmural pressure. Human resistance arteries were dissected from subcutaneous fat biopsies, mounted on a perfusion myograph, and imaged at varying transmural pressures using a multimodal nonlinear microscope. High-resolution three-dimensional images of elastic fibers, collagen, and cell nuclei were constructed. The honeycomb structure of the elastic fibers comprising the internal elastic layer became visible at a tr...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Bell, J. S., Adio, A. O., Pitt, A., Hayman, L., Thorn, C. E., Shore, A. C., Whatmore, J. L., Winlove, C. P. Tags: VASCULAR BIOLOGY AND MICROCIRCULATION Source Type: research

FOXO3a regulates BNIP3 and modulates mitochondrial calcium, dynamics, and function in cardiac stress
The forkhead box O3a (FOXO3a) transcription factor has been shown to regulate glucose metabolism, muscle atrophy, and cell death in postmitotic cells. Its role in regulation of mitochondrial and myocardial function is not well studied. Based on previous work, we hypothesized that FOXO3a, through BCL2/adenovirus E1B 19-kDa protein-interacting protein 3 (BNIP3), modulates mitochondrial morphology and function in heart failure (HF). We modulated the FOXO3a-BNIP3 pathway in normal and phenylephrine (PE)-stressed adult cardiomyocytes (ACM) in vitro and developed a cardiotropic adeno-associated virus serotype 9 encoding dominant...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Chaanine, A. H., Kohlbrenner, E., Gamb, S. I., Guenzel, A. J., Klaus, K., Fayyaz, A. U., Nair, K. S., Hajjar, R. J., Redfield, M. M. Tags: SIGNALING AND STRESS RESPONSE Source Type: research

Limitations of skeletal muscle oxygen delivery and utilization during moderate-intensity exercise in moderately impaired patients with chronic heart failure
This study examined the physiological background of submaximal exercise performance in 19 moderately impaired patients with CHF (Weber class A, B, and C) compared with 19 matched healthy control (HC) subjects by measuring skeletal muscle oxygenation (SmO2) changes during cycling exercise. All subjects performed two subsequent moderate-intensity 6-min exercise tests (bouts 1 and 2) with measurements of pulmonary oxygen uptake kinetics and SmO2 using near-infrared spatially resolved spectroscopy at the vastus lateralis for determination of absolute oxygenation values, amplitudes, kinetics (mean response time for onset), and ...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Niemeijer, V. M., Spee, R. F., Schoots, T., Wijn, P. F. F., Kemps, H. M. C. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Dietary nitrate supplementation attenuates the reduction in exercise tolerance following blood donation
We tested the hypothesis that dietary nitrate (NO3–)-rich beetroot juice (BR) supplementation could partially offset deteriorations in O2 transport and utilization and exercise tolerance after blood donation. Twenty-two healthy volunteers performed moderate-intensity and ramp incremental cycle exercise tests prior to and following withdrawal of ~450 ml of whole blood. Before donation, all subjects consumed seven 70-ml shots of NO3–-depleted BR [placebo (PL)] in the 48 h preceding the exercise tests. During the 48 h after blood donation, subjects consumed seven shots of BR (each containing 6.2 mmol of NO3–...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: McDonagh, S. T. J., Vanhatalo, A., Fulford, J., Wylie, L. J., Bailey, S. J., Jones, A. M. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Physiological and hypoxic oxygen concentration differentially regulates human c-Kit+ cardiac stem cell proliferation and migration
This study provides novel insights into the modulatory effects of O2 concentration on CSC biology and has important implications for refining stem cell therapies. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Bellio, M. A., Rodrigues, C. O., Landin, A. M., Hatzistergos, K. E., Kuznetsov, J., Florea, V., Valasaki, K., Khan, A., Hare, J. M., Schulman, I. H. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Fluid mechanics of human fetal right ventricles from image-based computational fluid dynamics using 4D clinical ultrasound scans
There are 0.6–1.9% of US children who were born with congenital heart malformations. Clinical and animal studies suggest that abnormal blood flow forces might play a role in causing these malformation, highlighting the importance of understanding the fetal cardiovascular fluid mechanics. We performed computational fluid dynamics simulations of the right ventricles, based on four-dimensional ultrasound scans of three 20-wk-old normal human fetuses, to characterize their flow and energy dynamics. Peak intraventricular pressure gradients were found to be 0.2–0.9 mmHg during systole, and 0.1–0.2 mmHg during d...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Wiputra, H., Lai, C. Q., Lim, G. L., Heng, J. J. W., Guo, L., Soomar, S. M., Leo, H. L., Biwas, A., Mattar, C. N. Z., Yap, C. H. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation
We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated. TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days postoperation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice. Cardiac magnetic resonance imaging showed no difference in infarct size and left ventr...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Omiya, S., Omori, Y., Taneike, M., Protti, A., Yamaguchi, O., Akira, S., Shah, A. M., Nishida, K., Otsu, K. Tags: INTEGRATIVE CARDIOVASCULAR PHYSIOLOGY AND PATHOPHYSIOLOGY Source Type: research

Spontaneous initiation of premature ventricular complexes and arrhythmias in type 2 long QT syndrome
The occurrence of early afterdepolarizations (EADs) and increased dispersion of repolarization are two known factors for arrhythmogenesis in long QT syndrome. However, increased dispersion of repolarization tends to suppress EADs due to the source-sink effect, and thus how the two competing factors cause initiation of arrhythmias remains incompletely understood. Here we used optical mapping and computer simulation to investigate the mechanisms underlying spontaneous initiation of arrhythmias in type 2 long QT (LQT2) syndrome. In optical mapping experiments of transgenic LQT2 rabbit hearts under isoproterenol, premature ven...
Source: AJP: Heart and Circulatory Physiology - December 1, 2016 Category: Cardiology Authors: Huang, X., Kim, T. Y., Koren, G., Choi, B.-R., Qu, Z. Tags: CARDIAC EXCITATION AND CONTRACTION Source Type: research