Imaging and modeling of acute pressure-induced changes of collagen and elastin microarchitectures in pig and human resistance arteries
In conclusion, we show here, for the first time in resistance arteries, a quantitative relationship between pressure-induced changes in the extracellular matrix and the arterial wall mechanics. The strength of the integrated methods invites for future detailed studies of microvascular pathologies. NEW & NOTEWORTHY This is the first study to quantitatively relate pressure-induced microstructural changes in resistance arteries to the mechanics of their wall. Principal findings using a pig model system were confirmed in human arteries. The combined methods provide a strong tool for future hypothesis-driven studies of micr...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Bloksgaard, M., Leurgans, T. M., Spronck, B., Heusinkveld, M. H. G., Thorsted, B., Rosenstand, K., Nissen, I., Hansen, U. M., Brewer, J. R., Bagatolli, L. A., Rasmussen, L. M., Irmukhamedov, A., Reesink, K. D., De Mey, J. G. R. Tags: RESEARCH ARTICLE Source Type: research

Cardiac hyporesponsiveness in severe sepsis is associated with nitric oxide-dependent activation of G protein receptor kinase
G protein-coupled receptor kinase isoform 2 (GRK2) has a critical role in physiological and pharmacological responses to endogenous and exogenous substances. Sepsis causes an important cardiovascular dysfunction in which nitric oxide (NO) has a relevant role. The present study aimed to assess the putative effect of inducible NO synthase (NOS2)-derived NO on the activity of GRK2 in the context of septic cardiac dysfunction. C57BL/6 mice were submitted to severe septic injury by cecal ligation and puncture (CLP). Heart function was assessed by isolated and perfused heart, echocardiography, and β-adrenergic receptor bind...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Dal-Secco, D., DalBo, S., Lautherbach, N. E. S., Gava, F. N., Celes, M. R. N., Benedet, P. O., Souza, A. H., Akinaga, J., Lima, V., Silva, K. P., Kiguti, L. R. A., Rossi, M. A., Kettelhut, I. C., Pupo, A. S., Cunha, F. Q., Assreuy, J. Tags: RESEARCH ARTICLE Source Type: research

Ultrasound biomicroscopy validation of a murine model of cardiac hypertrophic preconditioning: comparison with a hemodynamic assessment
In mice, myocardial hypertrophic preconditioning (HP), which is produced by the removal of short-term transverse aortic constriction (TAC), was recently reported to render the heart resistant to hypertrophic responses induced by subsequent reconstriction (Re-TAC). However, there is no efficient noninvasive method for ensuring that the repeated aortic manipulations were successfully performed. We previously demonstrated that ultrasound biomicroscopy (UBM) is a noninvasive and effective approach for predicting TAC success. Here, we investigated the value of UBM for serial predictions of load conditions in establishing a muri...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Huang, J., Wu, J., Wang, S., You, J., Ye, Y., Ding, Z., Yang, F., Wang, X., Guo, J., Ma, L., Yuan, J., Shen, Y., Yang, X., Sun, A., Jiang, H., Bu, L., Backx, P. H., Ge, J., Zou, Y. Tags: RESEARCH ARTICLE Source Type: research

Quantitative cardiac phosphoproteomics profiling during ischemia-reperfusion in an immature swine model
Ischemia-reperfusion (I/R) results in altered metabolic and molecular responses, and phosphorylation is one of the most noted regulatory mechanisms mediating signaling mechanisms during physiological stresses. To expand our knowledge of the potential phosphoproteomic changes in the myocardium during I/R, we used Isobaric Tags for Relative and Absolute Quantitation-based analyses in left ventricular samples obtained from porcine hearts under control or I/R conditions. The data are available via ProteomeXchange with identifier PXD006066. We identified 1,896 phosphopeptides within left ventricular control and I/R porcine samp...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Ledee, D., Kang, M. A., Kajimoto, M., Purvine, S., Brewer, H., Pasa-Tolic, L., Portman, M. A. Tags: RESEARCH ARTICLE Source Type: research

VO2 kinetics associated with moderate-intensity exercise in heart failure: impact of intrathecal fentanyl inhibition of group III/IV locomotor muscle afferents
This study revealed that abnormal musculoskeletal–neural afferents couple with pulmonary and circulatory dysfunction to provoke impaired exercise Vo2 in HF. Steady-state Vo2 cannot properly phenotype abnormal muscle afferent contributions to impaired exercise Vo2 in HF. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Van Iterson, E. H., Johnson, B. D., Joyner, M. J., Curry, T. B., Olson, T. P. Tags: RESEARCH ARTICLE Source Type: research

Cardiac myofibrillar contractile properties during the progression from hypertension to decompensated heart failure
Heart failure arises, in part, from a constellation of changes in cardiac myocytes including remodeling, energetics, Ca2+ handling, and myofibrillar function. However, little is known about the changes in myofibrillar contractile properties during the progression from hypertension to decompensated heart failure. The aim of the present study was to provide a comprehensive assessment of myofibrillar functional properties from health to heart disease. A rodent model of uncontrolled hypertension was used to test the hypothesis that myocytes in compensated hearts exhibit increased force, higher rates of force development, faste...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Hanft, L. M., Emter, C. A., McDonald, K. S. Tags: RESEARCH ARTICLE Source Type: research

Interaction of 12/15-lipoxygenase with fatty acids alters the leukocyte kinetics leading to improved postmyocardial infarction healing
In conclusion, deletion of 12/15-LOX and short-term exposure of PUFA promoted leukocyte clearance, thereby limiting cardiac remodeling and promoting an effective resolution of inflammation. NEW & NOTEWORTHY This study determined that 1) deletion of 12/15-lipoxygenase (LOX) promotes the generation of epoxyeicosatrienoic acids, the cytochrome P-450-derived metabolites in postmyocardial infarction (post-MI) healing; 2) acute exposure of fatty acids to 12/15-LOX–/– mice drives leukocyte (neutrophils and macrophages) clearance post-MI; and 3) metabolic transformation of fats is the significant contributor in leu...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Halade, G. V., Kain, V., Ingle, K. A., Prabhu, S. D. Tags: RESEARCH ARTICLE Source Type: research

Molecular effects of exercise training in patients with cardiovascular disease: focus on skeletal muscle, endothelium, and myocardium
For decades, we have known that exercise training exerts beneficial effects on the human body, and clear evidence is available that a higher fitness level is associated with a lower incidence of suffering premature cardiovascular death. Despite this knowledge, it took some time to also incorporate physical exercise training into the treatment plan for patients with cardiovascular disease (CVD). In recent years, in addition to continuous exercise training, further training modalities such as high-intensity interval training and pyramid training have been introduced for coronary artery disease patients. The beneficial effect...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Adams, V., Reich, B., Uhlemann, M., Niebauer, J. Tags: REVIEW Source Type: research

S-nitrosylation of VASP at cysteine 64 mediates the inflammation-stimulated increase in microvascular permeability
We tested the hypothesis that platelet-activating factor (PAF) induces S-nitrosylation of vasodilator-stimulated phosphoprotein (VASP) as a mechanism to reduce microvascular endothelial barrier integrity and stimulate hyperpermeability. PAF elevated S-nitrosylation of VASP above baseline levels in different endothelial cells and caused hyperpermeability. To ascertain the importance of endothelial nitric oxide synthase (eNOS) subcellular location in this process, we used ECV-304 cells transfected with cytosolic eNOS (GFPeNOSG2A) and plasma membrane eNOS (GFPeNOSCAAX). PAF induced S-nitrosylation of VASP in cells with cytoso...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Zamorano, P., Marin, N., Cordova, F., Aguilar, A., Meininger, C., Boric, M. P., Golenhofen, N., Contreras, J. E., Sarmiento, J., Duran, W. N., Sanchez, F. A. Tags: RAPID REPORT Source Type: research

Acute beetroot juice supplementation on sympathetic nerve activity: a randomized, double-blind, placebo-controlled proof-of-concept study
Acute dietary nitrate (NO3–) supplementation reduces resting blood pressure in healthy normotensives. This response has been attributed to increased nitric oxide bioavailability and peripheral vasodilation, although nitric oxide also tonically inhibits central sympathetic outflow. We hypothesized that acute dietary NO3– supplementation using beetroot (BR) juice would reduce blood pressure and muscle sympathetic nerve activity (MSNA) at rest and during exercise. Fourteen participants (7 men and 7 women, age: 25 ± 10 yr) underwent blood pressure and MSNA measurements before and after (165–180 min) in...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Notay, K., Incognito, A. V., Millar, P. J. Tags: RAPID REPORT Source Type: research

MK5 haplodeficiency attenuates hypertrophy and preserves diastolic function during remodeling induced by chronic pressure overload in the mouse heart
MAPK-activated protein kinase-5 (MK5) is a protein serine/threonine kinase that is activated by p38 MAPK and the atypical MAPKs ERK3 and ERK4. The physiological function(s) of MK5 remains unknown. Here, we examined the effect of MK5 haplodeficiency on cardiac function and myocardial remodeling. At 12 wk of age, MK5 haplodeficient mice (MK5+/–) were smaller than age-matched wild-type littermates (MK5+/+), with similar diastolic function but reduced systolic function. Transverse aortic constriction (TAC) was used to induce chronic pressure overload in 12-wk-old male MK5+/– and MK5+/+ mice. Two weeks post-TAC, hea...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Nawaito, S. A., Dingar, D., Sahadevan, P., Hussein, B., Sahmi, F., Shi, Y., Gillis, M.-A., Gaestel, M., Tardif, J.-C., Allen, B. G. Tags: RESEARCH ARTICLE Source Type: research

Desmin loss and mitochondrial damage precede left ventricular systolic failure in volume overload heart failure
This study provides new evidence of early onset (24 h) and continuous (4–12 wk) desmin misarrangement and disruption of the normal sarcomeric and mitochondrial architecture throughout the progression of volume overload heart failure, suggesting a causal link between desmin cleavage and mitochondrial disorganization and damage. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Guichard, J. L., Rogowski, M., Agnetti, G., Fu, L., Powell, P., Wei, C.-C., Collawn, J., DellItalia, L. J. Tags: RESEARCH ARTICLE Source Type: research

Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia
This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans. NEW & NOTEWORTHY Shear stress dilates the internal carotid artery in humans. This vasodilatory response occurs independent of other physiological factors, as demonstrated by our transient CO2 test, and is strongly correlated to shear area under the curve. Assessing carotid shear-mediated dilation may provide a future avenue for assessing cerebrovascular health and the risk of cerebrovascular events. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Hoiland, R. L., Smith, K. J., Carter, H. H., Lewis, N. C. S., Tymko, M. M., Wildfong, K. W., Bain, A. R., Green, D. J., Ainslie, P. N. Tags: RESEARCH ARTICLE Source Type: research

Hypoxia-mediated regulation of the secretory properties of mitral valve interstitial cells
In conclusion, hypoxia affects the production of certain ECM proteins and expression of matrix remodeling enzymes by MVICs. The effects of hypoxia appear to correlate with the induction of HIF-1α. This study highlights a potential role of hypoxia and HIF-1α in regulating the mitral valve, which could be important in health and disease. NEW & NOTEWORTHY This study demonstrates that hypoxia regulates extracellular matrix secretion and the remodeling potential of heart valve interstitial cells. Expression of hypoxia-induced factor-1α plays a role in these effects. These data highlight the potential role ...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Salhiyyah, K., Sarathchandra, P., Latif, N., Yacoub, M. H., Chester, A. H. Tags: RESEARCH ARTICLE Source Type: research

Vasculopathy in the setting of cardiorenal syndrome: roles of protein-bound uremic toxins
Chronic kidney disease (CKD) often leads to and accelerates the progression of cardiovascular disease (CVD), while CVD also causes kidney dysfunction. This bidirectional interaction leads to the development of a complex syndrome known as cardiorenal syndrome (CRS). CRS not only involves both the heart and the kidney but also the vascular system through a vast array of contributing factors. In addition to hemodynamic, neurohormonal, mechanical, and biochemical factors, nondialyzable protein-bound uremic toxins (PBUTs) are also key contributing factors that have been demonstrated through in vitro, in vivo, and clinical obser...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Guo, J., Lu, L., Hua, Y., Huang, K., Wang, I., Huang, L., Fu, Q., Chen, A., Chan, P., Fan, H., Liu, Z.-M., Wang, B. H. Tags: REVIEW Source Type: research