Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms
Conclusions PCSK9 increases hepatic lipid and lipoprotein production via apoE- and LDLR-dependent mechanisms. However, hPCSK9 also accumulate in the artery wall and directly affects atherosclerosis lesion size and composition independently of such plasma lipid and lipoprotein changes. These effects of hPCSK9 are dependent on LDLR but are independent of apoE. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Tavori, H., Giunzioni, I., Predazzi, I. M., Plubell, D., Shivinsky, A., Miles, J., Devay, R. M., Liang, H., Rashid, S., Linton, M. F., Fazio, S. Tags: Vascular Biology Source Type: research

miR-199-sponge transgenic mice develop physiological cardiac hypertrophy
Conclusion Inhibition of endogenous miR-199 led to physiological cardiac hypertrophy probably due to the up-regulation of PGC1α, uncovering a surprising role for endogenous miR-199 in the maintenance of cardiac homeostasis. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Li, Z., Liu, L., Hou, N., Song, Y., An, X., Zhang, Y., Yang, X., Wang, J. Tags: Cardiac biology and remodelling Source Type: research

Normalization of cardiac substrate utilization and left ventricular hypertrophy precede functional recovery in heart failure regression
Aims Impaired cardiac substrate metabolism plays an important role in heart failure (HF) pathogenesis. Since many of these metabolic changes occur at the transcriptional level of metabolic enzymes, it is possible that this loss of metabolic flexibility is permanent and thus contributes to worsening cardiac function and/or prevents the full regression of HF upon treatment. However, despite the importance of cardiac energetics in HF, it remains unclear whether these metabolic changes can be normalized. In the current study, we investigated whether a reversal of an elevated aortic afterload in mice with severe HF would result...
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Byrne, N. J., Levasseur, J., Sung, M. M., Masson, G., Boisvenue, J., Young, M. E., Dyck, J. R. B. Tags: Cardiac biology and remodelling Source Type: research

Profilin modulates sarcomeric organization and mediates cardiomyocyte hypertrophy
Conclusion Our results identify novel roles for profilin as an important mediator of cardiomyocyte hypertrophy. We show that overexpression of profilin is sufficient to induce cardiomyocyte hypertrophy and sarcomeric remodelling, and silencing of profilin attenuates the hypertrophic response. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Kooij, V., Viswanathan, M. C., Lee, D. I., Rainer, P. P., Schmidt, W., Kronert, W. A., Harding, S. E., Kass, D. A., Bernstein, S. I., Van Eyk, J. E., Cammarato, A. Tags: Cardiac biology and remodelling Source Type: research

Kcne2 deletion attenuates acute post-ischaemia/reperfusion myocardial infarction
Aims Most cardiac arrhythmia-associated genes encode ion channel subunits and regulatory proteins that are also expressed outside the heart, suggesting that diseases linked to their disruption may be multifactorial. KCNE2 is a ubiquitously expressed potassium channel β subunit associated with cardiac arrhythmia, atherosclerosis, and myocardial infarction (MI) in human populations. Here, we tested the hypothesis that Kcne2 disruption in mice would influence the acute outcome of experimentally induced MI. Methods and results One-year-old male Kcne2+/+ and Kcne2–/– mice were subjected to cardiac ischaemia/re...
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Hu, Z., Crump, S. M., Zhang, P., Abbott, G. W. Tags: Cardiac biology and remodelling Source Type: research

miR-21 promotes fibrosis in an acute cardiac allograft transplantation model
Conclusion Thus, inhibition of miR-21 is a novel strategy to target fibrosis development in cardiac allografts. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Gupta, S. K., Itagaki, R., Zheng, X., Batkai, S., Thum, S., Ahmad, F., Van Aelst, L. N., Sharma, A., Piccoli, M.-T., Weinberger, F., Fiedler, J., Heuser, M., Heymans, S., Falk, C. S., Förster, R., Schrepfer, S., Thum, T. Tags: Cardiac biology and remodelling Source Type: research

Selective phosphorylation of PKA targets after {beta}-adrenergic receptor stimulation impairs myofilament function in Mybpc3-targeted HCM mouse model
Conclusion These data provide evidence that in the KI HCM mouse model, β-AR stimulation leads to preferential PKA phosphorylation of PLN over cTnI, resulting in an impaired inotropic and lusitropic response. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Najafi, A., Sequeira, V., Helmes, M., Bollen, I. A. E., Goebel, M., Regan, J. A., Carrier, L., Kuster, D. W. D., Van Der Velden, J. Tags: Cardiac biology and remodelling Source Type: research

Carfilzomib reverses pulmonary arterial hypertension
Conclusion The addition of anti-tumour agents such as CFZ along with cardioprotectants to currently available vasodilators may be a promising way to improve PAH therapy. (Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Wang, X., Ibrahim, Y. F., Das, D., Zungu-Edmondson, M., Shults, N. V., Suzuki, Y. J. Tags: Integrative physiology and pathophysiology Source Type: research

Lack of MG53 in human heart precludes utility as a biomarker of myocardial injury or endogenous cardioprotective factor
Aims Mitsugumin-53 (MG53/TRIM72) is an E3-ubiquitin ligase that rapidly accumulates at sites of membrane injury and plays an important role in membrane repair of skeletal and cardiac muscle. MG53 has been implicated in cardiac ischaemia–reperfusion injury, and serum MG53 provides a biomarker of skeletal muscle injury in the mdx mouse model of Duchenne muscular dystrophy. We evaluated the clinical utility of MG53 as a biomarker of myocardial injury. Methods and results We performed Langendorff ischaemia–reperfusion injury on wild-type and dysferlin-null murine hearts, using dysferlin deficiency to effectively m...
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Lemckert, F. A., Bournazos, A., Eckert, D. M., Kenzler, M., Hawkes, J. M., Butler, T. L., Ceely, B., North, K. N., Winlaw, D. S., Egan, J. R., Cooper, S. T. Tags: Integrative physiology and pathophysiology Source Type: research

Micro-RNAs in abdominal aortic aneurysms: insights from animal models and relevance to human disease
Abdominal aortic aneurysm (AAA) is a major health concern and may be associated with high rates of mortality linked to acute complications. Diagnosis and treatment are, respectively, based on imaging and surgical techniques. Drug-based therapies are still mostly ineffective, which highlight a real unmet need. Major pathophysiological mechanisms leading to aneurysm formation involve inflammatory processes, degradation of the extracellular matrix, and loss of smooth muscle cells. However, the precise cellular and molecular pathways are still poorly understood. Recently, microRNAs have emerged as major intracellular players i...
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Raffort, J., Lareyre, F., Clement, M., Mallat, Z. Tags: REVIEW Source Type: research

Complexity of cardiac ion channel macromolecular complexes
(Source: Cardiovascular Research)
Source: Cardiovascular Research - April 19, 2016 Category: Cardiology Authors: Mohler, P. J., Abriel, H. Tags: EDITORIAL Source Type: research

Calmodulin kinase II inhibition limits the pro-arrhythmic Ca2+ waves induced by cAMP-phosphodiesterase inhibitors
Conclusion Our results show that PDE inhibitors exert inotropic effects via PKA but lead to SCWs via both PKA and CaMKII activation partly via Epac2, suggesting the potential use of CaMKII inhibitors as adjuncts to PDE inhibition to limit their pro-arrhythmic effects. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Bobin, P., Varin, A., Lefebvre, F., Fischmeister, R., Vandecasteele, G., Leroy, J. Tags: Ion Channels and Arrhythmias Source Type: research

MicroRNA-10a/10b represses a novel target gene mib1 to regulate angiogenesis
Conclusion Taken together, these results indicate that miR-10 regulates the angiogenic behaviour in a Notch-dependent manner by directly targeting mib1. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Wang, X., Ling, C. C., Li, L., Qin, Y., Qi, J., Liu, X., You, B., Shi, Y., Zhang, J., Jiang, Q., Xu, H., Sun, C., You, Y., Chai, R., Liu, D. Tags: Vascular Biology Source Type: research

THSD1 preserves vascular integrity and protects against intraplaque haemorrhaging in ApoE-/- mice
Conclusion THSD1 is a new regulator of endothelial barrier function during vascular development and protects intraplaque microvessels against haemorrhaging in advanced atherosclerotic lesions. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Haasdijk, R. A., Den Dekker, W. K., Cheng, C., Tempel, D., Szulcek, R., Bos, F. L., Hermkens, D. M. A., Chrifi, I., Brandt, M. M., Van Dijk, C., Xu, Y. J., Van De Kamp, E. H. M., Blonden, L. A. J., Van Bezu, J., Sluimer, J. C., Biessen, E. A. L., Van Nieu Tags: Vascular Biology Source Type: research

Counteractive effects of omentin-1 against atherogenesis
Conclusion This study provided the first evidence that omentin-1 may serve as a novel therapeutic target for atherosclerosis and CAD. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Watanabe, K., Watanabe, R., Konii, H., Shirai, R., Sato, K., Matsuyama, T.-a., Ishibashi-Ueda, H., Koba, S., Kobayashi, Y., Hirano, T., Watanabe, T. Tags: Vascular Biology Source Type: research

Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice
Conclusion These data document for the first time that omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Hiramatsu-Ito, M., Shibata, R., Ohashi, K., Uemura, Y., Kanemura, N., Kambara, T., Enomoto, T., Yuasa, D., Matsuo, K., Ito, M., Hayakawa, S., Ogawa, H., Otaka, N., Kihara, S., Murohara, T., Ouchi, N. Tags: Vascular Biology Source Type: research

Additive cardioprotection by pharmacological postconditioning with hydrogen sulfide and nitric oxide donors in mouse heart: S-sulfhydration vs. S-nitrosylation
In this study, we examined whether there are changes in protein SSH associated with cardioprotection induced by treatment with H2S on reperfusion. In addition, we also examined whether there is cross talk between H2S and NO. Compared with control, treatment on reperfusion with NaHS (H2S donor, 100 µmol/L) significantly reduced post-ischaemic contractile dysfunction and infarct size. A comparable cardioprotective effect could be also achieved by reperfusion treatment with SNAP (NO donor, 10 µmol/L). Interestingly, simultaneous reperfusion with both donors had an additive protective effect. In addition, C-PTIO (N...
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Sun, J., Aponte, A. M., Menazza, S., Gucek, M., Steenbergen, C., Murphy, E. Tags: Cardiac biology and remodelling Source Type: research

Ataxia telangiectasia mutated in cardiac fibroblasts regulates doxorubicin-induced cardiotoxicity
Conclusion ATM-regulated effects within cardiac fibroblasts are pivotal in Dox-induced cardiotoxicity, and antagonism of ATM and its functions may have potential therapeutic implications. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Zhan, H., Aizawa, K., Sun, J., Tomida, S., Otsu, K., Conway, S. J., Mckinnon, P. J., Manabe, I., Komuro, I., Miyagawa, K., Nagai, R., Suzuki, T. Tags: Cardiac biology and remodelling Source Type: research

Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways
Conclusions This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Crippa, S., Nemir, M., Ounzain, S., Ibberson, M., Berthonneche, C., Sarre, A., Boisset, G., Maison, D., Harshman, K., Xenarios, I., Diviani, D., Schorderet, D., Pedrazzini, T. Tags: Cardiac biology and remodelling Source Type: research

Cardiac hypertrophy is exacerbated in aged mice lacking the osteoprotegerin gene
Conclusion These results suggest that OPG plays a role in preserving myocardial structure and function with ageing through a reduction in apoptosis and preservation of the matrix structure. In addition, this appears to be independent of effects on the vasculature. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Hao, Y., Tsuruda, T., Sekita-Hatakeyama, Y., Kurogi, S., Kubo, K., Sakamoto, S., Nakamura, M., Udagawa, N., Sekimoto, T., Hatakeyama, K., Chosa, E., Asada, Y., Kitamura, K. Tags: Cardiac biology and remodelling Source Type: research

Temporal neutrophil polarization following myocardial infarction
Conclusion This study is the first to identify the existence of N1 and N2 neutrophils in the infarct region and reveals that N1 polarization could be mediated by DAMPs. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Ma, Y., Yabluchanskiy, A., Iyer, R. P., Cannon, P. L., Flynn, E. R., Jung, M., Henry, J., Cates, C. A., Deleon-Pennell, K. Y., Lindsey, M. L. Tags: Cardiac biology and remodelling Source Type: research

Expression and function of Kv7.4 channels in rat cardiac mitochondria: possible targets for cardioprotection
Conclusion Kv7.4 channels are present and functional in cardiac mitochondria; their activation exerts a significant cardioprotective role, making them potential therapeutic targets against I/R-induced cardiac injury. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Testai, L., Barrese, V., Soldovieri, M. V., Ambrosino, P., Martelli, A., Vinciguerra, I., Miceli, F., Greenwood, I. A., Curtis, M. J., Breschi, M. C., Sisalli, M. J., Scorziello, A., Canduela, M. J., Grandes, P., Calderone, V., Taglialatela, M. Tags: Cardiac biology and remodelling Source Type: research

Modulators of right ventricular apoptosis and contractility in a rat model of pulmonary hypertension
Conclusion These results suggest that RV decompensation is associated with the death of cardiomyocytes, resulting in fibrosis. However, the remaining myocytes are capable of sustaining RV contractility through the mechanism that involves CSQ2. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Zungu-Edmondson, M., Shults, N. V., Wong, C.-M., Suzuki, Y. J. Tags: Integrative physiology and pathophysiology Source Type: research

Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol
Conclusion In conclusion, our study demonstrates a dose-dependent physiological effect of human IDOL on LDL metabolism in mice. This provides a potential model for preclinical testing of IDOL inhibitors for reduction of LDL-C levels. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Ibrahim, S., Somanathan, S., Billheimer, J., Wilson, J. M., Rader, D. J. Tags: Integrative physiology and pathophysiology Source Type: research

The multifactorial nature of microRNAs in vascular remodelling
Vascular remodelling is a multifactorial process that involves both adaptive and maladaptive changes of the vessel wall through, among others, cell proliferation and migration, but also apoptosis and necrosis of the various cell types in the vessel wall. Vascular remodelling can be beneficial, e.g. during neovascularization after ischaemia, as well as pathological, e.g. during atherosclerosis and aneurysm formation. In recent years, it has become clear that microRNAs are able to target many genes that are involved in vascular remodelling processes and either can promote or inhibit structural changes of the vessel wall. Sin...
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Welten, S. M. J., Goossens, E. A. C., Quax, P. H. A., Nossent, A. Y. Tags: REVIEW Source Type: research

Mitochondrial potassium homeostasis: a central player in cardioprotection
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: Schulz, R., Di Lisa, F. Tags: EDITORIALS Source Type: research

Corrigendum to: Role of common and rare variants in SCN10A: results from the Brugada syndrome QRS locus gene discovery collaborative study
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Tags: CORRIGENDUM Source Type: research

Atheroprotective properties of human Omentin-1 in experimental atherosclerosis
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Authors: De Jager, S. C. A., Pasterkamp, G. Tags: EDITORIALS Source Type: research

Editorial Board
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Cover Page
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Contents Page
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Aims and Scope
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 18, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Atrial remodelling in atrial fibrillation: CaMKII as a nodal proarrhythmic signal
CaMKII is a serine–threonine protein kinase that is abundant in myocardium. Emergent evidence suggests that CaMKII may play an important role in promoting atrial fibrillation (AF) by targeting a diverse array of proteins involved in membrane excitability, cell survival, calcium homeostasis, matrix remodelling, inflammation, and metabolism. Furthermore, CaMKII inhibition appears to protect against AF in animal models and correct proarrhythmic, defective intracellular Ca2+ homeostasis in fibrillating human atrial cells. This review considers current concepts and evidence from animal and human studies on the role of CaM...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Mesubi, O. O., Anderson, M. E. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Atrial metabolism and tissue perfusion as determinants of electrical and structural remodelling in atrial fibrillation
Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation waves. Far less is known about the role of myocyte metabolism and tissue perfusion in the pathogenesis of AF. However, the rapid rates of electrical activity and contraction during AF must present an enormous challenge to the energy balance of atrial myocytes. This challenge can be met by scaling back energy deman...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Opacic, D., van Bragt, K. A., Nasrallah, H. M., Schotten, U., Verheule, S. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Keeping up the balance: role of HDACs in cardiac proteostasis and therapeutic implications for atrial fibrillation
Cardiomyocytes are long-lived post-mitotic cells with limited regenerative capacity. Proper cardiomyocyte function depends critically on the maintenance of a healthy homeostasis of protein expression, folding, assembly, trafficking, function, and degradation, together commonly referred to as proteostasis. Impairment of proteostasis has a prominent role in the pathophysiology of ageing-related neurodegenerative diseases including Huntington's, Parkinson's, and Alzheimer's disease. Emerging evidence reveals also a role for impaired proteostasis in the pathophysiology of common human cardiac diseases such as cardiac hypertrop...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Zhang, D., Hu, X., Henning, R. H., Brundel, B. J. J. M. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Compromised redox homeostasis, altered nitroso-redox balance, and therapeutic possibilities in atrial fibrillation
Although the initiation, development, and maintenance of atrial fibrillation (AF) have been linked to alterations in myocyte redox state, the field lacks a complete understanding of the impact these changes may have on cellular signalling, atrial electrophysiology, and disease progression. Recent studies demonstrate spatiotemporal changes in reactive oxygen species production shortly after the induction of AF in animal models with an uncoupling of nitric oxide synthase activity ensuing in the presence of long-standing persistent AF, ultimately leading to a major shift in nitroso–redox balance. However, it remains unc...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Simon, J. N., Ziberna, K., Casadei, B. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Cardiac adipose tissue and atrial fibrillation: the perils of adiposity
The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contrib...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Hatem, S. N., Redheuil, A., Gandjbakhch, E. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Common variation in atrial fibrillation: navigating the path from genetic association to mechanism
Atrial fibrillation (AF) is the most common cardiac arrhythmia with well-established clinical and genetic risk components. Genome-wide association studies (GWAS) have identified 17 independent susceptibility signals for AF at 14 genomic regions, but the mechanisms through which these loci confer risk to AF remain largely undefined. This problem is not unique to AF, as the field of functional genomics, which attempts to bridge this gap from genotype to phenotype, has only uncovered the mechanisms for a handful of GWAS loci. Recent functional genomic studies have made great strides towards translating genetic discoveries to ...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Tucker, N. R., Clauss, S., Ellinor, P. T. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Presence and stability of rotors in atrial fibrillation: evidence and therapeutic implications
We report and discuss discrepancies regarding rotor prevalence and stability in various studies, which can be attributed in part to methodological differences among mapping systems. Future research for validation and improvement of current clinical electrophysiology mapping technologies will be crucial for developing mechanistic-based selection and application of the best therapeutic strategy for individual AF patient, being it, pharmaceutical, ablative, or other approach. (Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Guillem, M. S., Climent, A. M., Rodrigo, M., Fernandez-Aviles, F., Atienza, F., Berenfeld, O. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

The value of basic research insights into atrial fibrillation mechanisms as a guide to therapeutic innovation: a critical analysis
Atrial fibrillation (AF) is an extremely common clinical problem associated with increased morbidity and mortality. Current antiarrhythmic options include pharmacological, ablation, and surgical therapies, and have significantly improved clinical outcomes. However, their efficacy remains suboptimal, and their use is limited by a variety of potentially serious adverse effects. There is a clear need for improved therapeutic options. Several decades of research have substantially expanded our understanding of the basic mechanisms of AF. Ectopic firing and re-entrant activity have been identified as the predominant mechanisms ...
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Heijman, J., Algalarrondo, V., Voigt, N., Melka, J., Wehrens, X. H. T., Dobrev, D., Nattel, S. Tags: INVITED SPOTLIGHT REVIEWS Source Type: research

Deciphering the fundamental mechanisms of atrial fibrillation: a quest for over a century
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Nattel, S., Dobrev, D. Tags: EDITORIALS Source Type: research

Spotlight on atrial fibrillation in Cardiovascular Research
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Authors: Sipido, K. R. Tags: EDITORIALS Source Type: research

Aims and Scope
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Editorial Board
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Cover Page
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Contents Page
(Source: Cardiovascular Research)
Source: Cardiovascular Research - March 4, 2016 Category: Cardiology Tags: FRONT-MATTER/BACK-MATTER Source Type: research

Pre-clinical studies in remote ischaemic conditioning: a solid foundation for on-going clinical research?
This editorial refers to ‘Remote ischaemic conditioning reduces infarct size in animal in vivo models of ischaemia-reperfusion injury: a systematic review and meta-analysis’ by D.I. Bromage et al., pp. 288–297. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 28, 2016 Category: Cardiology Source Type: research

L-type Cav1.3 channels regulate ryanodine receptor-dependent Ca2+ release during sino-atrial node pacemaker activity
Conclusions Cav1.3 channels play a critical role in the regulation of [Ca2+]i dynamics, providing an unanticipated mechanism for triggering local [Ca2+]i releases and thereby controlling pacemaker activity. Our study also provides an additional pathophysiological mechanism for congenital SAN dysfunction and heart block linked to Cav1.3 loss of function in humans. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 12, 2016 Category: Cardiology Authors: Torrente, A. G., Mesirca, P., Neco, P., Rizzetto, R., Dubel, S., Barrere, C., Sinegger-Brauns, M., Striessnig, J., Richard, S., Nargeot, J., Gomez, A. M., Mangoni, M. E. Tags: Ion Channels and Arrhythmias Source Type: research

TBX5 mutations contribute to early-onset atrial fibrillation in Chinese and Caucasians
Conclusion Our results provide both genetic and functional evidence to support the contribution of TBX5 gene in the pathogenesis of AF. The potential mechanism of arrhythmia may be due in part to the disturbed expression of ANP and CX40. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 12, 2016 Category: Cardiology Authors: Ma, J.-F., Yang, F., Mahida, S. N., Zhao, L., Chen, X., Zhang, M. L., Sun, Z., Yao, Y., Zhang, Y.-X., Zheng, G.-Y., Dong, J., Feng, M.-J., Zhang, R., Sun, J., Li, S., Wang, Q.-S., Cao, H., Benjamin, E. J., Ellinor, P. T., Li, Y.-G., Tian, X.-L. Tags: Ion Channels and Arrhythmias Source Type: research

Pitx2c increases in atrial myocytes from chronic atrial fibrillation patients enhancing IKs and decreasing ICa,L
Conclusion Our results demonstrated for the first time that CAF increases Pitx2c expression in isolated human atrial myocytes and suggested that this transcription factor could contribute to the CAF-induced IKs increase and ICa,L reduction observed in humans. (Source: Cardiovascular Research)
Source: Cardiovascular Research - February 12, 2016 Category: Cardiology Authors: Perez-Hernandez, M., Matamoros, M., Barana, A., Amoros, I., Gomez, R., Nunez, M., Sacristan, S., Pinto, A., Fernandez-Aviles, F., Tamargo, J., Delpon, E., Caballero, R. Tags: Ion Channels and Arrhythmias Source Type: research