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Article ; Online: Endogenous cardiotonic steroids and cardiovascular disease, where to next?

Pavlovic, Davor

2019 Volume 86, Page(s) 102156

Abstract: Ever since British Physician William Withering first described the use of foxglove extract for treatment of patients with congestive heart failure in 1785, cardiotonic steroids have been used clinically to treat heart failure and more recently atrial ... ...

Abstract	Ever since British Physician William Withering first described the use of foxglove extract for treatment of patients with congestive heart failure in 1785, cardiotonic steroids have been used clinically to treat heart failure and more recently atrial fibrillation. Due to their ability to bind and inhibit the ubiquitous transport enzyme sodium potassium pump, thus regulating intracellular Na
MeSH term(s)	Animals ; Cardiac Glycosides/biosynthesis ; Cardiac Glycosides/chemistry ; Cardiac Glycosides/metabolism ; Cardiovascular Diseases/metabolism ; Cardiovascular Diseases/physiopathology ; Humans ; Models, Biological ; Signal Transduction ; Sodium-Potassium-Exchanging ATPase
Chemical Substances	Cardiac Glycosides ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
Language	English
Publishing date	2019-12-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	757687-0
ISSN	1532-1991 ; 0143-4160
ISSN (online)	1532-1991
ISSN	0143-4160
DOI	10.1016/j.ceca.2019.102156
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Article ; Online: What is actually preserved in HFpEF? Focus on myocyte calcium handling remodelling.

Johnson, Daniel M / Pavlovic, Davor

Journal of molecular and cellular cardiology

2022 Volume 170, Page(s) 115–116

MeSH term(s)	Calcium ; Heart Failure ; Heart Ventricles ; Humans ; Muscle Cells ; Stroke Volume
Chemical Substances	Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-06-15
Publishing country	England
Document type	Letter
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2022.06.002
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Zs.A 426: Show issues

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Article ; Online: Mouse cardiomyocyte isolation: Filling the age gaps.

Ackers-Johnson, Matthew / Foo, Roger S / Pavlovic, Davor

Journal of molecular and cellular cardiology

2022 Volume 170, Page(s) 124–125

MeSH term(s)	Animals ; Mice ; Myocytes, Cardiac
Language	English
Publishing date	2022-07-09
Publishing country	England
Document type	Editorial ; Research Support, Non-U.S. Gov't
ZDB-ID	80157-4
ISSN	1095-8584 ; 0022-2828
ISSN (online)	1095-8584
ISSN	0022-2828
DOI	10.1016/j.yjmcc.2022.07.001
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Zs.A 426: Show issues

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Article ; Online: The role of cardiotonic steroids in the pathogenesis of cardiomyopathy in chronic kidney disease.

Pavlovic, Davor

Nephron. Clinical practice

2014 Volume 128, Issue 1-2, Page(s) 11–21

Abstract: Cardiotonic steroids (CTS) are a new class of hormones that circulate in the blood and are divided into two distinct groups, cardenolides, such as ouabain and digoxin, and bufadienolides, such as marinobufagenin, telocinobufagin and bufalin. They have ... ...

Abstract	Cardiotonic steroids (CTS) are a new class of hormones that circulate in the blood and are divided into two distinct groups, cardenolides, such as ouabain and digoxin, and bufadienolides, such as marinobufagenin, telocinobufagin and bufalin. They have the ability to bind and inhibit the ubiquitous transport enzyme sodium potassium pump, thus regulating intracellular Na(+) concentration in every living cell. Although digoxin has been prescribed to heart failure patients for at least 200 years, the realization that CTS are endogenously produced has intensified research into their physiological and pathophysiological roles. Over the last two decades, substantial evidence has accumulated demonstrating the effects of endogenously synthesised CTS on the kidneys, vasculature and the heart. In this review, the current state of art and the controversies surrounding the manner in which CTS mediate their pathophysiological effects are discussed. Several potential therapeutic strategies have emerged as a result of our increased understanding of the role CTS play in health and disease.
MeSH term(s)	Cardiac Glycosides/metabolism ; Cardiovascular Diseases/etiology ; Humans ; Ion Transport ; Kidney Failure, Chronic/complications ; Renal Insufficiency, Chronic/complications ; Signal Transduction
Chemical Substances	Cardiac Glycosides
Language	English
Publishing date	2014
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	207121-6
ISSN	1660-2110 ; 1423-0186 ; 2235-3186 ; 1660-8151 ; 0028-2766
ISSN (online)	1660-2110 ; 1423-0186 ; 2235-3186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000363301
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Zs.A 169: Show issues

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Article ; Online: Complex Relationship Between Cardiac Fibroblasts and Cardiomyocytes in Health and Disease.

Hall, Caitlin / Gehmlich, Katja / Denning, Chris / Pavlovic, Davor

Journal of the American Heart Association

2021 Volume 10, Issue 5, Page(s) e019338

Abstract: Cardiac fibroblasts are the primary cell type responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signaling processes. Despite the importance of ... ...

Abstract	Cardiac fibroblasts are the primary cell type responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signaling processes. Despite the importance of fibrosis in processes of wound healing, excessive fibroblast proliferation and activation can lead to pathological remodeling, driving heart failure and the onset of arrhythmias. Our understanding of the mechanisms driving the cardiac fibroblast activation and proliferation is expanding, and evidence for their direct and indirect effects on cardiac myocyte function is accumulating. In this review, we focus on the importance of the fibroblast-to-myofibroblast transition and the cross talk of cardiac fibroblasts with cardiac myocytes. We also consider the current use of models used to explore these questions.
MeSH term(s)	Animals ; Cells, Cultured ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Heart Failure/metabolism ; Heart Failure/pathology ; Humans ; Myocytes, Cardiac/metabolism ; Myocytes, Cardiac/pathology ; Signal Transduction
Language	English
Publishing date	2021-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.120.019338
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Article ; Online: Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.

Baines, Olivia / Sha, Rina / Kalla, Manish / Holmes, Andrew P / Efimov, Igor R / Pavlovic, Davor / O'Shea, Christopher

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology

2024 Volume 26, Issue 2

Abstract: State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed ... ...

Abstract	State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell-cell interactions. The merging of optogenetics and optical mapping techniques for 'all-optical' electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial-temporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies.
MeSH term(s)	Humans ; Electrophysiologic Techniques, Cardiac/methods ; Optogenetics/methods ; Cardiac Electrophysiology/methods ; Heart ; Arrhythmias, Cardiac/therapy
Language	English
Publishing date	2024-01-13
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	1449879-0
ISSN	1532-2092 ; 1099-5129
ISSN (online)	1532-2092
ISSN	1099-5129
DOI	10.1093/europace/euae017
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Zs.A 5434: Show issues

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Article ; Online: Hypertension and cardiomyopathy associated with chronic kidney disease: epidemiology, pathogenesis and treatment considerations.

Law, Jonathan P / Pickup, Luke / Pavlovic, Davor / Townend, Jonathan N / Ferro, Charles J

Journal of human hypertension

2022 Volume 37, Issue 1, Page(s) 1–19

Abstract: Chronic kidney disease (CKD) is a complex condition with a prevalence of 10-15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. ... ...

Abstract	Chronic kidney disease (CKD) is a complex condition with a prevalence of 10-15% worldwide. An inverse-graded relationship exists between cardiovascular events and mortality with kidney function which is independent of age, sex, and other risk factors. The proportion of deaths due to heart failure and sudden cardiac death increase with progression of chronic kidney disease with relatively fewer deaths from atheromatous, vasculo-occlusive processes. This phenomenon can largely be explained by the increased prevalence of CKD-associated cardiomyopathy with worsening kidney function. The key features of CKD-associated cardiomyopathy are increased left ventricular mass and left ventricular hypertrophy, diastolic and systolic left ventricular dysfunction, and profound cardiac fibrosis on histology. While these features have predominantly been described in patients with advanced kidney disease on dialysis treatment, patients with only mild to moderate renal impairment already exhibit structural and functional changes consistent with CKD-associated cardiomyopathy. In this review we discuss the key drivers of CKD-associated cardiomyopathy and the key role of hypertension in its pathogenesis. We also evaluate existing, as well as developing therapies in the treatment of CKD-associated cardiomyopathy.
MeSH term(s)	Humans ; Renal Insufficiency, Chronic/complications ; Renal Insufficiency, Chronic/epidemiology ; Renal Insufficiency, Chronic/therapy ; Kidney ; Hypertension/complications ; Hypertension/epidemiology ; Hypertension/therapy ; Cardiomyopathies/epidemiology ; Cardiomyopathies/etiology ; Cardiomyopathies/therapy ; Ventricular Dysfunction, Left ; Hypertrophy, Left Ventricular/epidemiology ; Hypertrophy, Left Ventricular/etiology ; Hypertrophy, Left Ventricular/therapy
Language	English
Publishing date	2022-09-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639472-3
ISSN	1476-5527 ; 0950-9240
ISSN (online)	1476-5527
ISSN	0950-9240
DOI	10.1038/s41371-022-00751-4
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Zs.A 2380: Show issues

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Article ; Online: The Role of Cardiotonic Steroids in the Pathogenesis of Cardiomyopathy in Chronic Kidney Disease

Pavlovic, Davor

Nephron Clinical Practice

2014 Volume 128, Issue 1-2, Page(s) 11–21

Abstract	Cardiotonic steroids (CTS) are a new class of hormones that circulate in the blood and are divided into two distinct groups, cardenolides, such as ouabain and digoxin, and bufadienolides, such as marinobufagenin, telocinobufagin and bufalin. They have the ability to bind and inhibit the ubiquitous transport enzyme sodium potassium pump, thus regulating intracellular Na+ concentration in every living cell. Although digoxin has been prescribed to heart failure patients for at least 200 years, the realization that CTS are endogenously produced has intensified research into their physiological and pathophysiological roles. Over the last two decades, substantial evidence has accumulated demonstrating the effects of endogenously synthesised CTS on the kidneys, vasculature and the heart. In this review, the current state of art and the controversies surrounding the manner in which CTS mediate their pathophysiological effects are discussed. Several potential therapeutic strategies have emerged as a result of our increased understanding of the role CTS play in health and disease.© 2014 S. Karger AG, Basel
Keywords	Cardiotonic steroids ; Chronic kidney disease ; End-stage renal disease ; Sodium potassium pump ; Ouabain ; Marinobufagenin ; Bufalin ; Telocinobufagin ; Digoxin
Language	English
Publisher	S. Karger AG
Publishing place	Basel
Publishing country	Switzerland
Document type	Article ; Online
ZDB-ID	207121-6
ISSN	1660-2110 ; 1423-0186 ; 0028-2766 ; 1660-2110 ; 0028-2766
ISSN (online)	1660-2110 ; 1423-0186
ISSN	1660-2110 ; 0028-2766
DOI	10.1159/000363301
Database	Karger publisher's database

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Zs.A 169: Show issues

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Article: The Role of Cardiotonic Steroids in the Pathogenesis of Cardiomyopathy in Chronic Kidney Disease

Pavlovic, Davor

Nephron Clinical Practice

2014 Volume 128, Issue 1-2, Page(s) 11–21

Institution	Cardiovascular Division, King's College London, Rayne Institute, St. Thomas' Hospital, London, UK
Abstract	Cardiotonic steroids (CTS) are a new class of hormones that circulate in the blood and are divided into two distinct groups, cardenolides, such as ouabain and digoxin, and bufadienolides, such as marinobufagenin, telocinobufagin and bufalin. They have the ability to bind and inhibit the ubiquitous transport enzyme sodium potassium pump, thus regulating intracellular Na concentration in every living cell. Although digoxin has been prescribed to heart failure patients for at least 200 years, the realization that CTS are endogenously produced has intensified research into their physiological and pathophysiological roles. Over the last two decades, substantial evidence has accumulated demonstrating the effects of endogenously synthesised CTS on the kidneys, vasculature and the heart. In this review, the current state of art and the controversies surrounding the manner in which CTS mediate their pathophysiological effects are discussed. Several potential therapeutic strategies have emerged as a result of our increased understanding of the role CTS play in health and disease.
Keywords	Marinobufagenin ; Bufalin ; Telocinobufagin ; Digoxin ; Ouabain ; Cardiotonic steroids ; Chronic kidney disease ; End-stage renal disease ; Sodium potassium pump
Language	English
Publishing date	2014-10-23
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Minireview
ZDB-ID	207121-6
ISSN	1660-2110 ; 1423-0186 ; 2235-3186 ; 1660-8151 ; 0028-2766
ISSN (online)	1660-2110 ; 1423-0186 ; 2235-3186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000363301
Database	Karger publisher's database

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Zs.A 169: Show issues

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Article ; Online: Impact of Obesity on Atrial Fibrillation Pathogenesis and Treatment Options.

Sha, Rina / Baines, Olivia / Hayes, Abbie / Tompkins, Katie / Kalla, Manish / Holmes, Andrew P / O'Shea, Christopher / Pavlovic, Davor

Journal of the American Heart Association

2023 Volume 13, Issue 1, Page(s) e032277

Abstract: Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like ... ...

Abstract	Atrial fibrillation (AF) is the most common cardiac arrhythmia. AF increases the risk of stroke, heart failure, dementia, and hospitalization. Obesity significantly increases AF risk, both directly and indirectly, through related conditions, like hypertension, diabetes, and heart failure. Obesity-driven structural and electrical remodeling contribute to AF via several reported mechanisms, including adiposity, inflammation, fibrosis, oxidative stress, ion channel alterations, and autonomic dysfunction. In particular, expanding epicardial adipose tissue during obesity has been suggested as a key driver of AF via paracrine signaling and direct infiltration. Weight loss has been shown to reverse these changes and reduce AF risk and recurrence after ablation. However, studies on how obesity affects pharmacologic or interventional AF treatments are limited. In this review, we discuss mechanisms by which obesity mediates AF and treatment outcomes, aiming to provide insight into obesity-drug interactions and guide personalized treatment for this patient subgroup.
MeSH term(s)	Humans ; Atrial Fibrillation/epidemiology ; Atrial Fibrillation/etiology ; Atrial Fibrillation/therapy ; Obesity/complications ; Obesity/epidemiology ; Obesity/therapy ; Treatment Outcome ; Adiposity ; Heart Failure
Language	English
Publishing date	2023-12-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.123.032277
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