Abstract：
:Protein kinase A (PKA) is a central regulator of cardiac performance and morphology. Myocardial PKA activation is induced by a variety of hormones, neurotransmitters and stress signals, most notably catecholamines secreted by the sympathetic nervous system. Catecholamines bind β-adrenergic receptors to stimulate cAMP-dependent PKA activation in cardiomyocytes. Elevated PKA activity enhances Ca2+ cycling and increases cardiac muscle contractility. Dynamic control of PKA is essential for cardiac homeostasis, as dysregulation of PKA signaling is associated with a broad range of heart diseases. Specifically, abnormal PKA activation or inactivation contributes to the pathogenesis of myocardial ischemia, hypertrophy, heart failure, as well as diabetic, takotsubo, or anthracycline cardiomyopathies. PKA may also determine sex-dependent differences in contractile function and heart disease predisposition. Here, we describe the recent advances regarding the roles of PKA in cardiac physiology and pathology, highlighting previous study limitations and future research directions. Moreover, we discuss the therapeutic strategies and molecular mechanisms associated with cardiac PKA biology. In summary, PKA could serve as a promising drug target for cardioprotection. Depending on disease types and mechanisms, therapeutic intervention may require either inhibition or activation of PKA. Therefore, specific PKA inhibitors or activators may represent valuable drug candidates for the treatment of heart diseases.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Liu Y,Chen J,Fontes SK,Bautista EN,Cheng Zdoi
10.1093/cvr/cvab008subject
Has Abstractpub_date
2021-01-23 00:00:00eissn
0008-6363issn
1755-3245pii
6105176pub_type
杂志文章abstract：OBJECTIVE:To characterise the effect of coronary intra-arterial thrombosis upon the downstream vascular bed. BACKGROUND:The vascular response downstream from a coronary intra-arterial thrombus has not previously been characterised. We postulated that downstream vasoconstriction might result from the presence of endoth...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：AIMS:During restenosis, vascular smooth muscle cells (VSMCs) migrate from the vascular media to the developing neointima. Preventing VSMC migration is therefore a therapeutic target for restenosis. Drugs, such as prostacyclin analogues, that increase the intracellular concentration of cyclic adenosine monophosphate (cA...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvv176
更新日期：2015-09-01 00:00:00
abstract：:An analytical formulation has been developed which allows the computation of mitral valve area (A) from the potentially noninvasive paramaeters of hear rate (R), cardiac output (CO) and diastolic filling period (DFP) by the equation A = 21 CO/R x DFP2. The computed areas correlate with autopsy and open heart measureme...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/14.4.223
更新日期：1980-04-01 00:00:00
abstract：OBJECTIVE:Inducible costimulator (ICOS) is a member of the CD28 family. Although inflammation is an essential pathological feature of myocarditis, the role of ICOS in myocarditis remains unclear. METHODS AND RESULTS:Lewis rats were immunized on day 0 with purified porcine cardiac myosin to establish experimental autoi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(03)00334-1
更新日期：2003-07-01 00:00:00
abstract：STUDY OBJECTIVE:The aim was to evaluate the thrombolytic efficacy of recombinant double chain tissue plasminogen activator (Duteplase, t-PA) given as a single intravenous bolus versus an infusion in a canine model of coronary arterial occlusion/reperfusion. DESIGN:Coronary arterial thrombi were induced by a copper coi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.3.184
更新日期：1991-03-01 00:00:00
abstract：OBJECTIVE:To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS:A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of tra...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00273-5
更新日期：2001-07-01 00:00:00
abstract：OBJECTIVES:Angiotensin converting enzyme (ACE) activity in the plasma does not change significantly with hypertension in two-kidney, one-clip hypertensive (2K-1C) rats. However, heart ACE activity and mRNA increase with hypertension. We measured the ACE activity and mRNA in hypertrophied hearts at different times after...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：OBJECTIVE:To study the intracellular pathways which mediate the inhibitory actions of adenosine on isoprenaline-stimulated calcium current (ICa) in atrioventricular (AV) nodal myocytes. METHODS:The whole-cell patch-clamp technique was used to record ICa from rabbit AV nodal cells, isolated by enzymatic and mechanical ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00043-6
更新日期：1997-05-01 00:00:00
abstract：OBJECTIVE:Evidence suggests important relationships among chronic inflammatory processes, endothelial dysfunction, hypertension and target organ damage. The present study examined the effects of chronic treatment with an anti-inflammatory p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-239063AN) in the N(omeg...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2004.12.021
更新日期：2005-04-01 00:00:00
abstract：OBJECTIVE:Ischaemia followed by reperfusion brings about a reduction in cardiac capillary cross-sectional dimensions which is consistent with constriction. The aim of this study was to test the hypothesis that the reduction in cardiac capillary dimensions that occurs in ischaemia and reperfusion is caused by endothelia...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(00)00173-5
更新日期：2000-11-01 00:00:00
abstract：AIMS:Human congenital heart disease linked to mutations in the homeobox transcription factor, NKX2-5, is characterized by cardiac anomalies, including atrial and ventricular septal defects as well as conduction and occasional defects in contractility. In the mouse, homozygous germline deletion of Nkx2-5 gene results in...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr037
更新日期：2011-07-15 00:00:00
abstract：:Diabetic cardiomyopathy is a term used to describe cardiac muscle damage-induced heart failure. Multiple structural and biochemical reasons have been suggested to induce this disorder. The most prominent feature of the diabetic myocardium is attenuated insulin signalling that reduces survival kinases (Akt), potentiall...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvs426
更新日期：2013-03-01 00:00:00
abstract：OBJECTIVE:This study tested the hypothesis that overproduction of endogenous nitric oxide (NO) during endotoxemia may modulate coronary autoregulation and myocardial reactive hyperemia. METHODS:Hearts of endotoxin-pretreated rats and controls were isolated and arranged for perfusion in a Langendorff preparation. Autor...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00132-6
更新日期：1997-08-01 00:00:00
abstract：OBJECTIVE:The aim was to investigate the effect of lowering external potassium on the sensitivity of the normal and hypertrophied rat heart to arrhythmias induced by increases in ventricular wall stress. METHODS:The isolated working heart model was used to compare hypertrophied hearts from the spontaneously hypertensi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：UNLABELLED:Recent investigations have established the feasibility of using exogenously delivered angiogenic growth factors to increase collateral artery development in animal models of myocardial and hindlimb ischemia. OBJECTIVE:Our aim was to evaluate the ability of a stabilized form of acidic fibroblast growth facto...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(03)00522-4
更新日期：2003-10-01 00:00:00
abstract：OBJECTIVES:To determine whether the cytokine cardiotrophin-1 (CT-1) can protect the adult heart against ischaemia/reperfusion when added either prior to ischaemia or at reperfusion. BACKGROUND:CT-1 has previously been shown to protect cultured embryonic or neonatal cardiocytes from cell death. To assess the therapeuti...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00531-4
更新日期：2002-03-01 00:00:00
abstract：OBJECTIVE:Intercellular adhesion molecule (ICAM)-1 is an immunoglobulin-like cell adhesion molecule expressed by several cell types, including proliferating vascular smooth muscle cells (VSMC). Cross-linking ICAM-1 on the surface of different cell types has previously been shown to cause an increase in cellular activat...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00207-3
更新日期：2001-06-01 00:00:00
abstract：:Physical training has been advocated to minimize the problems associated with coronary heart disease; however, the responsible mechanisms are obscure. Rats trained to run on a treadmill were subjected to acute conditions of hypoxia and myocardial ischaemia. Trained rats were better able to maintain a higher level of c...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/10.3.359
更新日期：1976-05-01 00:00:00
abstract：:Severe sepsis and septic shock, which are among the most common causes of death in intensive care units worldwide, cause high morbidity, mortality, and social and economic costs. Therefore, developing successful therapies against sepsis is one of the most important challenges in critical care medicine. Death from sept...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvq317
更新日期：2011-02-15 00:00:00
abstract：OBJECTIVE:Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role...
journal_title：Cardiovascular research
pub_type： 临床试验,杂志文章
doi：10.1093/cvr/27.8.1477
更新日期：1993-08-01 00:00:00
abstract：OBJECTIVE:Atrial (ANP) and B-type natriuretics peptides (BNP) via their guanylyl cyclase-A (GC-A) receptor not only regulate arterial blood pressure and volume but also exert local antihypertrophic, antifibrotic and lusitropic effects in the heart. To elucidate whether cardiac hypertrophy/insufficiency and reversal is ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2004.07.004
更新日期：2004-11-01 00:00:00
abstract：AIMS:This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta. METHODS AND RESULTS:Aortic segments from orchidectomized and control male Sprague-Dawley ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvm059
更新日期：2008-02-01 00:00:00
abstract：:The heart contains not only cardiomyocytes but also other cell types such as endothelial cells and fibroblasts. Functional crosstalk among these cell types is important for normal cardiac function and is also involved in disease pathophysiology. Recent data indicate that redox signalling within and between endothelial...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvu050
更新日期：2014-05-01 00:00:00
abstract：BACKGROUND:Clinical trials suggest that sotalol and dofetilide are much more effective in preventing atrial fibrillation (AF) than in terminating it. This study evaluated potential mechanisms of discordant sotalol and dofetilide effects on AF termination vs. prevention. METHODS:We applied 240-electrode epicardial mapp...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(00)00320-5
更新日期：2001-04-01 00:00:00
abstract：OBJECTIVE:The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects. METHODS:Transmembrane action potentials and electrograms were recorded fr...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/28.11.1662
更新日期：1994-11-01 00:00:00
abstract：:A growing body of animal studies provides evidence for potential cardioprotective effects of inhibitors of the enzyme phosphodiesterase isoform 5. Infarct size reduction by administration of phosphodiesterase 5 inhibitors was described in various experimental models of ischaemia and reperfusion. Furthermore, potential...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvp170
更新日期：2009-07-15 00:00:00
abstract：:The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by bi...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvs081
更新日期：2012-05-01 00:00:00
abstract：AIMS:In obesity, chronic low-grade inflammation and overproduction of reactive oxygen species (ROS) in fat contribute to the development of metabolic syndrome. Suppression of inflammation and ROS production in fat may attenuate the metabolic syndrome. Activation of mineralocorticoid receptor (MR) promotes inflammation ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvp191
更新日期：2009-10-01 00:00:00
abstract：OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2007.07.001
更新日期：2007-11-01 00:00:00
abstract：OBJECTIVE:The mechanosensitive nonselective cation channel (NSC(MS)) and endothelin-1 (ET-1) play critical roles in the regulation of vascular tone. This study was undertaken to investigate the effect of ET-1 on NSC(MS) and on the myogenic response of arteries. METHODS:Cell-attached patch-clamp techniques were applied...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2007.06.021
更新日期：2007-11-01 00:00:00
