Abstract：
:The second messengers, cAMP and cGMP, regulate a number of physiological processes in the myocardium, from acute contraction/relaxation to chronic gene expression and cardiac structural remodeling. Emerging evidence suggests that multiple spatiotemporally distinct pools of cyclic nucleotides can discriminate specific cellular functions from a given cyclic nucleotide-mediated signal. Cyclic nucleotide phosphodiesterases (PDEs), by hydrolyzing intracellular cyclic AMP and/or cyclic GMP, control the amplitude, duration, and compartmentation of cyclic nucleotide signaling. To date, more than 60 different isoforms have been described and grouped into 11 broad families (PDE1-PDE11) based on differences in their structure, kinetic and regulatory properties, as well as sensitivity to chemical inhibitors. In the heart, PDE isozymes from at least six families have been investigated. Studies using selective PDE inhibitors and/or genetically manipulated animals have demonstrated that individual PDE isozymes play distinct roles in the heart by regulating unique cyclic nucleotide signaling microdomains. Alterations of PDE activity and/or expression have also been observed in various cardiac disease models, which may contribute to disease progression. Several family-selective PDE inhibitors have been used clinically or pre-clinically for the treatment of cardiac or vascular-related diseases. In this review, we will highlight both recent advances and discrepancies relevant to cardiovascular PDE expression, pathophysiological function, and regulation. In particular, we will emphasize how these properties influence current and future development of PDE inhibitors for the treatment of pathological cardiac remodeling and dysfunction.
journal_name
J Cardiovasc Transl Resjournal_title
Journal of cardiovascular translational researchauthors
Miller CL,Yan Cdoi
10.1007/s12265-010-9203-9subject
Has Abstractpub_date
2010-10-01 00:00:00pages
507-15issue
5eissn
1937-5387issn
1937-5395journal_volume
3pub_type
杂志文章,评审abstract：:The M protein of rheumatogenic group A streptococci induces carditis and valvulitis in Lewis rats and may play a role in pathogenesis of rheumatic heart disease. To identify the epitopes of M5 protein that produce valvulitis, synthetic peptides spanning A, B, and C repeat regions contained within the extracellular dom...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-013-9526-4
更新日期：2014-03-01 00:00:00
abstract：:COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and ...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-020-10031-6
更新日期：2020-12-01 00:00:00
abstract：:Different arrhythmogenic substrates for atrial fibrillation (AF) may underlie aortic valve (AV) and mitral valve (MV) disease. We located conduction disorders during sinus rhythm by high-resolution epicardial mapping in patients undergoing AV (n = 85) or MV (n = 54) surgery. Extent and distribution of conduction delay...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-019-09936-8
更新日期：2020-08-01 00:00:00
abstract：:Intercellular communication mediated by exosomes, nano-sized extracellular vesicles, is crucial for preserving vascular integrity and in the development of cardiovascular and other diseases. As natural carriers of signal molecules, exosomes released from sources such as blood cells, endothelial cells, immune cells, sm...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-016-9682-4
更新日期：2016-06-01 00:00:00
abstract：:Across biomedicine, there is a major drive to develop stem cell (SC) treatments for debilitating diseases. Most effective treatments restore an embryonic phenotype to adult SCs. This has led to two emerging paradigms in SC biology: the application of developmental biology studies and the manipulation of the SC niche. ...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-012-9386-3
更新日期：2012-10-01 00:00:00
abstract：:With improved screening and the advent of many novel therapeutics, patients with cancer are living longer and often surviving their disease. Cardiovascular complications have significant impact on both short- and long-term morbidity and mortality in these patients. While a great deal of attention has been paid to card...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-019-09924-y
更新日期：2020-06-01 00:00:00
abstract：:The field of myocardial regeneration utilizing novel cell-based therapies, gene transfer, and growth factors may prove to play an important role in the future management of ischemic heart disease and cardiomyopathy. Phases I and II clinical trials have been published for a variety of biologics utilizing four methods o...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-010-9253-z
更新日期：2011-04-01 00:00:00
abstract：:Valvular heart disease and congenital heart defects represent a major cause of death around the globe. Although current therapy strategies have rapidly evolved over the decades and are nowadays safe, effective, and applicable to many affected patients, the currently used artificial prostheses are still suboptimal. The...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-017-9728-2
更新日期：2017-04-01 00:00:00
abstract：:Heart failure is a worldwide pandemic influencing 26 million individuals worldwide and is expanding. Imbalanced redox homeostasis in cardiac cells alters the structure and function of the cells, which leads to contractile dysfunction, myocardial hypertrophy, and fibrosis in chronic heart failure. Various targets and a...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-020-10083-8
更新日期：2020-11-25 00:00:00
abstract：:Over the past decade, several longitudinal epidemiological studies have brought attention to the haptoglobin genotype and its importance in determining diabetic vascular disease risk. This manuscript presents an overview of the biology of the haptoglobin genotype and reviews the literature concerning its role in the d...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-012-9361-z
更新日期：2012-08-01 00:00:00
abstract：:Left ventricular outflow tract obstruction (LVOTO) is one of the defining features of hypertrophic cardiomyopathy (HCM) and one of the main determinants of prognosis. Although the importance of obstruction was recognized since the original description by Teare and Brock, its exact cause and methods for its relief are ...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-009-9153-2
更新日期：2009-12-01 00:00:00
abstract：:The clinical success of left ventricular assist devices (LVADs) has been tempered by significant hemorrhagic and thromboembolic complications. In the case of LVADs, where the biomaterial is in direct contact with the blood circulation, significant changes in systemic immunologic and thrombostatic functions have been w...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-008-9072-7
更新日期：2009-03-01 00:00:00
abstract：:Apoptosis of endothelial cells (ECs) has been suggested to play a role in atherosclerosis. We studied the synergism of hypercholesterolemia with Chlamydia pneumoniae and influenza virus infections on EC morphology and intimal changes in a minipig model. The coronary artery was excised at euthanasia (19 weeks of age) a...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-013-9463-2
更新日期：2013-08-01 00:00:00
abstract：:Thoracic aortic aneurysm (TAA) is a genetic disease predisposing to aortic dissection. It is important to identify the genetic modifiers controlling penetrance and expressivity to improve clinical prognostication. Exome sequencing was performed in 27 subjects with syndromic or familial TAA presenting with extreme phen...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-017-9753-1
更新日期：2017-08-01 00:00:00
abstract：:The Seventh International Symposium on Stem Cell Therapy and Cardiovascular Innovations was held in Madrid on the 6th and 7th of May 2010. Gathering for the seventh consecutive year the most relevant researchers and opinion leaders on cardiovascular cell therapy, it has become the most important worldwide event on thi...
journal_title：Journal of cardiovascular translational research
pub_type：
doi：10.1007/s12265-010-9247-x
更新日期：2011-04-01 00:00:00
abstract：:The implantation of ventricular assist devices (VADs) is a valuable option in patients with end-stage heart failure. The number of VAD implantations is growing worldwide. Between July 1987 and July 2010, we implanted 1,598 VADs in 1,455 patients. The majority were male (81.0%), and their mean age was 49.4 years (range...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-011-9268-0
更新日期：2011-06-01 00:00:00
abstract：:Diseases of the electrical conduction system that lead to irregularities in cardiac rhythm can have morbid and often lethal clinical outcomes. Linkage analysis has been the principal tool used to discover the genetic mutations responsible for Mendelian arrhythmic disease. Although the majority of arrhythmias can be ac...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-008-9030-4
更新日期：2008-06-01 00:00:00
abstract：:Heart failure (HF) and type 2 diabetes mellitus (T2DM) exhibit a well-established interrelationship and a growing prevalence, in particular in elderly people. Cardiac resynchronization therapy (CRT) has been shown to improve myocardial function in patients with HF and cardiac dyssynchrony. However, reports on CRT in d...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-014-9545-9
更新日期：2014-04-01 00:00:00
abstract：:Using unipolar atrial electrogram morphology as guidance for ablative therapy is regaining interest. Although standardly used in clinical practice during ablative therapy, the impact of filter settings on morphology of unipolar AF potentials is unknown. Thirty different filters were applied to 2,557,045 high-resolutio...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-020-10011-w
更新日期：2020-12-01 00:00:00
abstract：:Graphical abstract. ...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-020-10077-6
更新日期：2020-10-13 00:00:00
abstract：:Variability of response to clopidogrel and prasugrel is a multifactorial process, with clinical consequences, and drug-drug interactions have been proposed as potential factors. Biological modulation of clopidogrel response has been demonstrated for atorvastatin and omeprazole. However, investigations assessing clinic...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-012-9442-z
更新日期：2013-06-01 00:00:00
abstract：:Cardiovascular disease affects 80 million people in the USA and is the leading cause of death. Significant limitations of current treatments necessitate the development of novel strategies. Cardiovascular tissue engineering is an emerging field focused on the development of biological substitutes to restore, maintain,...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-007-9005-x
更新日期：2008-03-01 00:00:00
abstract：:The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, u...
journal_title：Journal of cardiovascular translational research
pub_type： 历史文章,杂志文章,实务指引,评审
doi：10.1007/s12265-015-9632-6
更新日期：2015-06-01 00:00:00
abstract：:Non-invasive means of evaluating appropriate cardiac unloading remain to be established. We hypothesized that myocardial deformation assessed by echocardiographic speckle-tracking strain analysis can reliably estimate the degree of left ventricular (LV) unloading under mechanical circulatory support. A total of 24 Yor...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章
doi：10.1007/s12265-018-9812-2
更新日期：2019-04-01 00:00:00
abstract：:The potency of specific transcription factors as cell fate determinants was first demonstrated by the discovery of MyoD, a master gene for skeletal muscle transdifferentiation. More recently, the induction of pluripotency in somatic cells using a combination of stem cell-specific transcription factors has been reporte...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-012-9412-5
更新日期：2013-02-01 00:00:00
abstract：:Sex differences in coronary artery disease (CAD) are well established, with women presenting with non-obstructive CAD more often than men do. However, recent evidence has identified coronary microvascular dysfunction as the underlying cause for cardiac complaints, yet sex-specific prevalence numbers are inconclusive. ...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-019-09906-0
更新日期：2020-02-01 00:00:00
abstract：:Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy with substantial heterogeneity in phenotypic expression and clinical course. Traditionally, two-dimensional echocardiography has been the easiest and most reliable technique for establishing a diagnosis of HCM. However, cardiovascular magnetic...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-009-9136-3
更新日期：2009-12-01 00:00:00
abstract：:Reperfusion injury may offset the optimal salvage of myocardium achieved during primary coronary angioplasty. Thus, coronary reperfusion must be combined with cardioprotective adjunctive therapies in order to optimize myocardial salvage and minimize infarct size. Forty-three patients with their first ST-elevation myoc...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,随机对照试验
doi：10.1007/s12265-010-9252-0
更新日期：2011-02-01 00:00:00
abstract：:Recently, a new surgical technique to rescue infarcted myocardium (AGTP) has already tested (NCT01473433, AdiFLAP Trial). Here, we present the new minimally invasive AGTP (mi-AGTP) by thoracoscopy. ...
journal_title：Journal of cardiovascular translational research
pub_type： 信件
doi：10.1007/s12265-016-9721-1
更新日期：2017-02-01 00:00:00
abstract：:Vascular smooth muscle cells (VSMCs) exhibit remarkable plasticity during postnatal development. Vascular injury initiates and perpetuates VSMCs dedifferentiation to a synthetic phenotype, which has been increasingly recognized to play a central role in neointimal hyperplasia during the pathogenesis of vascular prolif...
journal_title：Journal of cardiovascular translational research
pub_type： 杂志文章,评审
doi：10.1007/s12265-010-9163-0
更新日期：2010-06-01 00:00:00
