Heart and Circulatory Physiology

In this Issue

November 2015; volume 309, issue 10

CALL FOR PAPERS | Cardiovascular Responses to Environmental Stress

CALL FOR PAPERS | Exercise Training in Cardiovascular Disease: Mechanisms and Outcomes

  • Regulation of cardiac microRNAs induced by aerobic exercise training during heart failure
    Rodrigo W. A. Souza, Geysson J. Fernandez, João P. Q. Cunha, Warlen P. Piedade, Luana C. Soares, Paula A. T. Souza, Dijon H. S. de Campos, Katashi Okoshi, Antonio C. Cicogna, Maeli Dal-Pai-Silva, Robson F. Carvalho

    This research article reveals that during heart failure, exercise training regulates the expression of a set of cardiac miRNAs that can modulate cardioprotective mechanisms through multiple genes involved in programmed cell death, TGF-β signaling, cellular metabolic processes, cytokine signaling, and cell morphogenesis.

  • Aerobic exercise training-induced changes in serum adropin level are associated with reduced arterial stiffness in middle-aged and older adults
    Shumpei Fujie, Natsuki Hasegawa, Koji Sato, Satoshi Fujita, Kiyoshi Sanada, Takafumi Hamaoka, Motoyuki Iemitsu

    Serum adropin level in middle-aged and older adults was elevated by aerobic exercise training. Additionally, serum adropin level was associated with exercise training-induced alteration of arterial stiffness and plasma NOx level. Thus the increase in adropin may participate in the exercise-induced reduction of arterial stiffness, mediated by NO bioavailability.

CALL FOR PAPERS | Mechanisms of Diastolic Dysfunction in Cardiovascular Disease

  • Afterload-induced diastolic dysfunction contributes to high filling pressures in experimental heart failure with preserved ejection fraction
    Sara Leite, Sara Rodrigues, Marta Tavares-Silva, José Oliveira-Pinto, Mohamed Alaa, Mahmoud Abdellatif, Dulce Fontoura, Inês Falcão-Pires, Thierry C. Gillebert, Adelino F. Leite-Moreira, André P. Lourenço

    In a highly controlled hemodynamic evaluation setup in experimental heart failure with preserved ejection fraction, we demonstrate that delayed relaxation independently explains end-diastolic pressure elevation during suddenly imposed afterload. This is an important contribution to understanding the response to exercise or hypertensive stress in preserved ejection fraction heart failure.

CALL FOR PAPERS | Small Vessels–Big Problems: Novel Insights into Microvascular Mechanisms of Diseases

  • Fluid shear stress upregulates placental growth factor in the vessel wall via NADPH oxidase 4
    Nabil A. Rashdan, Pamela G. Lloyd

    Here we provide the first direct demonstration that the arteriogenic mediator placental growth factor is regulated by fluid shear stress (a physiological stimulus for collateral artery remodeling) in both vascular cell cocultures and isolated perfused arterioles. We further identify NADPH oxidase 4 and H2O2 as downstream mediators of this response.

Vascular Biology and Microcirculation

  • IFN-β affects the angiogenic potential of circulating angiogenic cells by activating calpain 1
    Cansu Yıldırım, Julie Favre, Ester M. Weijers, Ruud D. Fontijn, Michiel H. van Wijhe, Sandra J. van Vliet, Reinier A. Boon, Pieter Koolwijk, Tineke C. T. M. van der Pouw Kraan, Anton J. G. Horrevoets

    The effect of interferon-β on angiogenic cells has not been studied before. Interferon-β selectively affected circulating angiogenic cell (CAC) morphology and corresponding integrin-fibronectin-dependent adhesive functions, leading to a reduced number of CACs in vitro. We have identified a potential downstream effector molecule of interferon-β in CACs that might explain the reduced number of CACs in vitro. In vivo, this could lead to inhibition of neovascularization due to reduction of the locally recruited CAC numbers.

  • Adaptive increases in expression and vasodilator activity of estrogen receptor subtypes in a blood vessel-specific pattern during pregnancy
    Karina M. Mata, Wei Li, Ossama M. Reslan, Waleed T. Siddiqui, Lauren A. Opsasnick, Raouf A. Khalil

    The present study describes pregnancy-associated increases in estrogen receptor (ER)-mediated endothelium-dependent relaxation in the aorta and inhibition of Ca2+ entry in the mesenteric artery. Increased vascular ERs could promote vasodilation, oppose vasoconstriction, and maintain normotension during normal pregnancy, and ER agonists should be examined for potential usefulness in reducing blood pressure in hypertensive pregnancy.

  • ACE2/Ang-(1–7)/Mas axis stimulates vascular repair-relevant functions of CD34+ cells
    Neha Singh, Shrinidh Joshi, Lirong Guo, Matthew B. Baker, Yan Li, Ronald K. Castellano, Mohan K. Raizada, Yagna P. R. Jarajapu

    Angiotensin-(1–7) or its analog NorLeu3-Ang-(1–7) and the putative angiotensin converting enzyme (ACE)2 activators, xanthenone and diminazene aceturate, stimulate migration and proliferation - functional signatures of vasoreparative potential - of human CD34+ cells. Angiotensin II, by stimulating the generation of reactive oxygen species from mononuclear cells, attenuates the functions of CD34+ cells.

Energetics and Metabolism

Muscle Mechanics and Ventricular Function

  • N-acetylcysteine reverses diastolic dysfunction and hypertrophy in familial hypertrophic cardiomyopathy
    Tanganyika Wilder, David M. Ryba, David F. Wieczorek, Beata M. Wolska, R. John Solaro

    Novel findings include reversal of established hypertrophy, left atrial dilation, and diastolic dysfunction in a model of HCM treated with the antioxidant N-acetylcysteine. This was associated with a reduction in S-glutathionylation of myofilament proteins, which was increased in untreated controls, a decrease in myofilament Ca2+ response, and hastening of cross-bridge kinetics.

Integrative Cardiovascular Physiology and Pathophysiology

  • Leptin decreases heart rate associated with increased ventricular repolarization via its receptor
    Yen-Chang Lin, Jianying Huang, Stan Hileman, Karen H. Martin, Robert Hull, Mary Davis, Han-Gang Yu

    Leptin is believed to increase heart rate via adrenergic receptor stimulation. We found evidence that leptin can exert local direct inhibition of heart rate and prolongation of QTc interval via its receptor. The findings offer better understanding of higher incidence of prolonged QT and sudden cardiac death in obesity.

  • Central-peripheral neural network interactions evoked by vagus nerve stimulation: functional consequences on control of cardiac function
    Jeffrey L. Ardell, Pradeep S. Rajendran, Heath A. Nier, Bruce H. KenKnight, J. Andrew Armour

    Vagus nerve stimulation-evoked changes in cardiac function reflect the dynamic interplay between direct activation of descending efferents and afferent-induced decreases in central parasympathetic drive to the heart. With increasing current, vagus nerve stimulation first activates afferent fibers and then descending parasympathetic efferent fibers, interactions that maintain cardiac stability.

  • Rate-dependent activation failure in isolated cardiac cells and tissue due to Na+ channel block
    Anthony Varghese, Anthony J. Spindler, David Paterson, Denis Noble

    We present in silico predictions confirmed in vitro showing the efficacy of class-I antiarrhythmic agents in slowing heart rate at doses well below their IC50 values. The results hinge on differences between isolated cells versus tissue, highlighting the importance of integrative biology in understanding how therapeutic drug doses work.

  • Sustained myocardial production of stromal cell-derived factor-1α was associated with left ventricular adverse remodeling in patients with myocardial infarction
    Manabu Uematsu, Toru Yoshizaki, Takuya Shimizu, Jun-ei Obata, Takamitsu Nakamura, Daisuke Fujioka, Kazuhiro Watanabe, Yosuke Watanabe, Kiyotaka Kugiyama

    This is the first clinical study to show that stromal cell-derived factor-1α produced in the infarcted myocardial lesion in the chronic phase has an association with left ventricular adverse remodeling and progressive dysfunction in patients with myocardial infarction.

  • Roles of store-operated Ca2+ channels in regulating cell cycling and migration of human cardiac c-kit+ progenitor cells
    Hui Che, Gang Li, Hai-Ying Sun, Guo-Sheng Xiao, Yan Wang, Gui-Rong Li

    The present study demonstrates that Ca2+ signaling through SOCE channels regulates cell cycling and migration via activating cyclin D1, cyclin E, and/or p-Akt in human cardiac c-kit+ cells. Understanding the regulation of these cellular functions by SOCE channels is beneficial for developing new approaches to improve myocardial repair/regeneration.

  • Sepiapterin prevents left ventricular hypertrophy and dilatory remodeling induced by pressure overload in rats
    Kei Yoshioka, Hajime Otani, Takayuki Shimazu, Masanori Fujita, Toshiji Iwasaka, Ichiro Shiojima

    Oral administration of sepiapterin, a substrate of the salvage pathway of tetrahydrobiopterin synthesis, prevents left ventricular hypertrophy and dilatory left ventricular remodeling by inhibiting nitric oxide synthase uncoupling and increasing bioavailable nitric oxide.