Cyp2c44 gene disruption is associated with increased hematopoietic stem cells: implication in chronic hypoxia-induced pulmonary hypertension
In conclusion, our results demonstrate that CYP2C44-derived 15-HETE plays a critical role in downregulating HSC proliferation and growth, because disruption of the Cyp2c44 gene increased HSCs that potentially contribute to chronic hypoxia-induced pulmonary arterial remodeling and occlusion. NEW & NOTEWORTHY This study demonstrates that cytochrome P-450 2C44 plays a critical role in controlling the phenotype of hematopoietic stem cells and that when this enzyme is knocked out, stem cells are differentiated. These stem cells give rise to increased circulating monocytes and macrophages and contribute to the pathogenesis o...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Hashimoto, R., Joshi, S. R., Jiang, H., Capdevila, J. H., McMurtry, I. F., Laniado Schwartzman, M., Gupte, S. A. Tags: RESEARCH ARTICLE Source Type: research

A novel, de novo mutation in the PRKAG2 gene: infantile-onset phenotype and the signaling pathway involved
PRKAG2 encodes the 2-subunit isoform of 5'-AMP-activated protein kinase (AMPK), a heterotrimeric enzyme with major roles in the regulation of energy metabolism in response to cellular stress. Mutations in PRKAG2 have been implicated in a unique hypertrophic cardiomyopathy (HCM) characterized by cardiac glycogen overload, ventricular preexcitation, and hypertrophy. We identified a novel, de novo PRKAG2 mutation (K475E) in a neonate with prenatal onset of HCM. We aimed to investigate the cellular impact, signaling pathways involved, and therapeutic options for K475E mutation using cells stably expressing human wild-type (WT)...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Xu, Y., Gray, A., Hardie, D. G., Uzun, A., Shaw, S., Padbury, J., Phornphutkul, C., Tseng, Y.-T. Tags: RESEARCH ARTICLE Source Type: research

Variability in coronary artery anatomy affects consistency of cardiac damage after myocardial infarction in mice
In conclusion, variation in MI size and LV function after LCA ligation in mice is difficult to avoid. Anatomic diversity of the LCA in mice leads to inconsistency in MI size and functional parameters, and this is independent of potential technical modifications made by the operator. NEW & NOTEWORTHY In the present study, we demonstrate that left coronary artery diversity in mice is one of the primary causes of variable myocardial infarction size and cardiac functional parameters in the left coronary artery ligation model. Recognition of anatomic diversity is essential to improve reliability and reproducibility in heart...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Chen, J., Ceholski, D. K., Liang, L., Fish, K., Hajjar, R. J. Tags: RESEARCH ARTICLE Source Type: research

Acetylation of mitochondrial proteins by GCN5L1 promotes enhanced fatty acid oxidation in the heart
Lysine acetylation is a reversible posttranslational modification and is particularly important in the regulation of mitochondrial metabolic enzymes. Acetylation uses acetyl-CoA derived from fuel metabolism as a cofactor, thereby linking nutrition to metabolic activity. In the present study, we investigated how mitochondrial acetylation status in the heart is controlled by food intake and how these changes affect mitochondrial metabolism. We found that there was a significant increase in cardiac mitochondrial protein acetylation in mice fed a long-term high-fat diet and that this change correlated with an increase in the a...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Thapa, D., Zhang, M., Manning, J. R., Guimaraes, D. A., Stoner, M. W., ODoherty, R. M., Shiva, S., Scott, I. Tags: RESEARCH ARTICLE Source Type: research

Role of thiosulfate in hydrogen sulfide-dependent redox signaling in endothelial cells
This report provides new evidence that different levels of exogenous thiosulfate dynamically change discrete sulfide biochemical metabolite bioavailability in endothelial cells under normoxia or hypoxia, acting in a slow manner to modulate sulfide metabolites. Moreover, our findings also reveal that thiosulfate surprisingly inhibits VEGF-dependent endothelial cell proliferation associated with a reduction in cystathionine--lyase protein levels. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Leskova, A., Pardue, S., Glawe, J. D., Kevil, C. G., Shen, X. Tags: RESEARCH ARTICLE Source Type: research

Cyp2c44-mediated decrease of 15-HETE exacerbates pulmonary hypertension
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Fülöp, G. A., Yabluchanskiy, A. Tags: EDITORIAL FOCUS Source Type: research

The PRKAG2 gene and hypertrophic cardiomyopathy: an energetically imbalanced relationship
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Calore, M. Tags: EDITORIAL FOCUS Source Type: research

VEGF-B: friend or foe to the heart in times of nutrient excess?
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Rowe, G. C., Young, M. E. Tags: EDITORIAL FOCUS Source Type: research

Noninvasive evaluation of left ventricular elastance according to pressure-volume curves modeling in arterial hypertension
In conclusion, Ees and V0 can be estimated noninvasively from modeling of the P-V curve during ejection. This approach was found to be reproducible and sensitive enough to detect an expected increase in LV contractility in hypertensive patients. Because of its noninvasive nature, this methodology may have clinical implications in various disease states. NEW & NOTEWORTHY The use of real-time three-dimensional echocardiography-derived left ventricular volumes in conjunction with carotid tonometry was found to be reproducible and sensitive enough to detect expected differences in left ventricular elastance in arterial hyp...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Bonnet, B., Jourdan, F., du Cailar, G., Fesler, P. Tags: RESEARCH ARTICLE Source Type: research

Myocardial overexpression of TIMP3 after myocardial infarction exerts beneficial effects by promoting angiogenesis and suppressing early proteolysis
In conclusion, optimal overexpression of TIMP3 can be a promising therapeutic approach to limit adverse post-MI remodeling by dually inhibiting early proteolysis and promoting angiogenesis. NEW & NOTEWORTHY Here, we report that tissue inhibitor of metalloproteinase 3 overexpression after myocardial infarction improves myocardial structural remodeling and function by promoting angiogenesis and inhibiting early proteolysis. This demonstrates the therapeutic potential of preserving the local balance of tissue inhibitor of metalloproteinase 3 in the heart given its diverse functions in modulating different processes involv...
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Takawale, A., Zhang, P., Azad, A., Wang, W., Wang, X., Murray, A. G., Kassiri, Z. Tags: RESEARCH ARTICLE Source Type: research

Why publish in the American Journal of Physiology-Heart and Circulatory Physiology?
(Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - August 1, 2017 Category: Cardiology Authors: Zucker, I. H., Lindsey, M. L., Delmar, M., De Windt, L. J., Des Rosiers, C., Diz, D. I., Hester, R. L., Jones, S. P., Kanagy, N. L., Kitakaze, M., Liao, R., Lopaschuk, G. D., Patel, K. P., Recchia, F. A., Sadoshima, J., Shah, A. M., Ungvari, Z., Benjamin, Tags: EDITORIAL Source Type: research

Chronic hypoxia attenuates the vasodilator efficacy of protein kinase G in fetal and adult ovine cerebral arteries
Long-term hypoxia (LTH) attenuates nitric oxide-induced vasorelaxation in ovine middle cerebral arteries. Because cGMP-dependent protein kinase (PKG) is an important mediator of NO signaling in vascular smooth muscle, we tested the hypothesis that LTH diminishes the ability of PKG to interact with target proteins and cause vasorelaxation. Prominent among proteins that regulate vascular tone is the large-conductance Ca2+-sensitive K+ (BK) channel, which is a substrate for PKG and is responsive to phosphorylation on multiple serine/threonine residues. Given the influence of these proteins, we also examined whether LTH attenu...
Source: AJP: Heart and Circulatory Physiology - July 6, 2017 Category: Cardiology Authors: Thorpe, R. B., Hubbell, M. C., Silpanisong, J., Williams, J. M., Pearce, W. J. Tags: RESEARCH ARTICLE Source Type: research

WNT5A regulates adipose tissue angiogenesis via antiangiogenic VEGF-A165b in obese humans
Experimental studies have suggested that Wingless-related integration site 5A (WNT5A) is a proinflammatory secreted protein that is associated with metabolic dysfunction in obesity. Impaired angiogenesis in fat depots has been implicated in the development of adipose tissue capillary rarefaction, hypoxia, inflammation, and metabolic dysfunction. We have recently demonstrated that impaired adipose tissue angiogenesis is associated with overexpression of antiangiogenic factor VEGF-A165b in human fat and the systemic circulation. In the present study, we postulated that upregulation of WNT5A is associated with angiogenic dysf...
Source: AJP: Heart and Circulatory Physiology - July 6, 2017 Category: Cardiology Authors: Karki, S., Ngo, D. T. M., Farb, M. G., Park, S. Y., Saggese, S. M., Hamburg, N. M., Carmine, B., Hess, D. T., Walsh, K., Gokce, N. Tags: RESEARCH ARTICLE Source Type: research

Sarcolemmal distribution of ICa and INCX and Ca2+ autoregulation in mouse ventricular myocytes
This study shows that in contrast to the rat, mouse ventricular Na+/Ca2+ exchange current density is lower in the t-tubules than in the surface sarcolemma and Ca2+ current is predominantly located in the t-tubules. As a consequence, the t-tubules play a role in recovery (autoregulation) from reduced, but not increased, sarcoplasmic reticulum Ca2+ release. (Source: AJP: Heart and Circulatory Physiology)
Source: AJP: Heart and Circulatory Physiology - July 6, 2017 Category: Cardiology Authors: Gadeberg, H. C., Kong, C. H. T., Bryant, S. M., James, A. F., Orchard, C. H. Tags: RESEARCH ARTICLE Source Type: research

Endothelial cAMP deactivates ischemia-reperfusion-induced microvascular hyperpermeability via Rap1-mediated mechanisms
Approaches to reduce excessive edema due to the microvascular hyperpermeability that occurs during ischemia-reperfusion (I/R) are needed to prevent muscle compartment syndrome. We tested the hypothesis that cAMP-activated mechanisms actively restore barrier integrity in postischemic striated muscle. We found, using I/R in intact muscles and hypoxia-reoxygenation (H/R, an I/R mimic) in human microvascular endothelial cells (HMVECs), that hyperpermeability can be deactivated by increasing cAMP levels through application of forskolin. This effect was seen whether or not the hyperpermeability was accompanied by increased mRNA ...
Source: AJP: Heart and Circulatory Physiology - July 1, 2017 Category: Cardiology Authors: Korayem, A. H., Mujica, P. E., Aramoto, H., Duran, R. G., Nepali, P. R., Kim, D. D., Harris, A. L., Sanchez, F. A., Duran, W. N. Tags: RESEARCH ARTICLE Source Type: research