Abstract：
AIMS:Doxorubicin (DOX) is a widely used and effective anti-cancer therapeutic. DOX treatment is associated with both acute and late onset cardiotoxicity, limiting its overall efficacy. Here, the impact of cardiomyocyte cell cycle activation was examined in a juvenile model featuring aspects of acute and late onset DOX cardiotoxicity. METHODS AND RESULTS:Two-week old MHC-cycD2 transgenic mice (which express cyclin D2 in postnatal cardiomyocytes and exhibit sustained cardiomyocyte cell cycle activity; D2 mice) and their wild type (WT) littermates received weekly DOX injections for 5 weeks (25 mg/kg cumulative dose). One week after the last DOX treatment (acute stage), cardiac function was suppressed in both groups. Acute DOX cardiotoxicity in D2 and WT mice was associated with similar increases in the levels of cardiomyocyte apoptosis and Ku70/Ku80 expression (markers of DNA damage and oxidative stress), as well as similar reductions in hypertrophic cardiomyocyte growth. Cardiac dysfunction persisted in WT mice for 13 weeks following the last DOX treatment (late stage) and was accompanied by increased levels of cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis. In contrast, D2 mice exhibited a progressive recovery in cardiac function, which was indistinguishable from saline-treated animals by 9 weeks following the last DOX treatment. Improved cardiac function was accompanied by reductions in the levels of late stage cardiomyocyte apoptosis, Ku expression, and myocardial fibrosis. CONCLUSION:These data suggest that cardiomyocyte cell cycle activity can promote recovery of cardiac function and preserve cardiac structure following DOX treatment.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Zhu W,Reuter S,Field LJdoi
10.1093/cvr/cvy273subject
Has Abstractpub_date
2019-04-15 00:00:00pages
960-965issue
5eissn
0008-6363issn
1755-3245pii
5181163journal_volume
115pub_type
杂志文章abstract：OBJECTIVE:Myogenic tone, which has a major role in the regulation of local blood flow, refers to the ability of vascular smooth muscle to adapt its contractility to changes in transmural pressure. Although Rho-kinase is involved in myogenic tone, the pathway involved remains unclear, especially concerning translocation...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.10.020
更新日期：2007-01-01 00:00:00
abstract：:The 'master regulatory factors' that position at the top of the genetic hierarchy of lineage determination have been a focus of intense interest, and have been investigated in various systems. Etv2/Etsrp71/ER71 is such a factor that is both necessary and sufficient for the development of haematopoietic and endothelial...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvx133
更新日期：2017-09-01 00:00:00
abstract：OBJECTIVE:Smooth muscle cell proliferation and migration are the predominant responses to intimal and medial injury after percutaneous transluminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that the antiproliferative effect of heparin in...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/27.7.1209
更新日期：1993-07-01 00:00:00
abstract：:Arterial blood pressures were measured simultaneously in the thoracic and abdominal aortas in the same conscious rats. Intravenous administration of sodium nitroprusside caused a greater fall in systolic blood pressure in the abdominal aorta than in the thoracic aorta, whereas intravenous administration of methoxamine...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/20.5.379
更新日期：1986-05-01 00:00:00
abstract：:Many observational studies and experimental and animal studies have demonstrated that estrogen therapy (ET) or hormone therapy (HT) significantly reduces the risk of coronary heart disease. Nonetheless, recent randomized controlled trials and the Nurses' Health Study in secondary prevention demonstrate trends toward a...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2005.12.004
更新日期：2006-04-01 00:00:00
abstract：STUDY OBJECTIVE:The aim was to evaluate the influence that centrally administered angiotensin-II has on the intrarenal renin-angiotensin system and renal sympathetic nerve activity. DESIGN:Renal responses to centrally administered angiotensin-II (10 micrograms) or saralasin (50 micrograms) were measured in anaesthetis...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.5.353
更新日期：1991-05-01 00:00:00
abstract：:Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly red...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/11.6.568
更新日期：1977-11-01 00:00:00
abstract：OBJECTIVES:Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally....
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.11.001
更新日期：2007-02-01 00:00:00
abstract：:Computation of indices of regional myocardial contractility such as the shortening, or the work done by or on a segment of myocardium in a single cardial cycle is tedious to perform manually, and complex interfacing and software is needed for digital computation. We describe the principles of an on-line, analogue devi...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/17.12.767
更新日期：1983-12-01 00:00:00
abstract：OBJECTIVES:To investigate the effect of alpha,beta(1) and beta(2) adrenergic receptor (AR) stimulation on coronary hemodynamics, myocardial oxygen consumption (M(v)O(2)) and metabolic substrate preference in advanced dilated cardiomyopathy (DCM). METHODS:We studied 19 conscious, instrumented dogs with pacing-induced D...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00490-4
更新日期：2002-02-01 00:00:00
abstract：AIMS:Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn140
更新日期：2008-09-01 00:00:00
abstract：OBJECTIVE:Mice with genetic disruption of the guanylyl cyclase-A (GC-A) receptor for atrial natriuretic peptide (ANP), have chronic arterial hypertension and marked cardiac hypertrophy. Intriguingly, despite pronounced remodeling, cardiac contractile functions and cardiomyocyte Ca(2+)-handling are preserved and even en...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.10.003
更新日期：2007-03-01 00:00:00
abstract：OBJECTIVE:Previous studies have shown that chronic cardiac denervation impairs myocardial glucose oxidation. To investigate this further we tested whether the tissue content of glucose transporters, activity of glycolytic enzymes or metabolic capacity of pyruvate dehydrogenase were altered. Moreover, we investigated wh...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00220-4
更新日期：1998-01-01 00:00:00
abstract：BACKGROUND:Nitric oxide (NO) attenuates neutrophil (PMN)-mediated damage, partly by inhibiting superoxide anion (O2-) generation and adherence to the coronary artery endothelium. L-Arginine is the endogenous substrate for production of NO via the NO synthase pathway. This study tested the hypothesis that the endogenous...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1996-01-01 00:00:00
abstract：OBJECTIVE:Increased expression of the cardiac natriuretic peptides (NP), atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) is observed during chronic hemodynamic overload. The mechanisms underlying this process are not fully understood. In vitro, endothelin 1 (ET-1) is a powerful stimulator of cardiac...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(00)00311-4
更新日期：2001-03-01 00:00:00
abstract：:The acute haemodynamic effects of taurine were studied in normal and in beta blocker (propranolol) or calcium antagonist (diltiazem) treated rabbits and in rabbits with experimentally produced chronic aortic regurgitation. The administration of taurine (25 mg.kg-1) did not affect heart rate and left ventricular end di...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/21.4.241
更新日期：1987-04-01 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：OBJECTIVES:While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed form...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-10-01 00:00:00
abstract：:Protein and lipid oxidation-mainly by mitochondrial reactive oxygen species (mtROS)-was proposed as a crucial determinant of health and lifespan. Angiotensin II (Ang II) enhances ROS production by activating NAD(P)H oxidase and uncoupling endothelial nitric oxide synthase (NOS). Ang II also stimulates mtROS production...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvq285
更新日期：2011-01-01 00:00:00
abstract：AIMS:The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via in...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvu184
更新日期：2014-10-01 00:00:00
abstract：:Segments of saphenous vein from patients undergoing coronary artery by-pass graft surgery were frozen in liquid nitrogen immediately on dissection (control), after stripping of the adventitia and side branch ligation (manipulation), after distention with blood (distention), or at completion of the last proximal anasto...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/19.6.326
更新日期：1985-06-01 00:00:00
abstract：OBJECTIVE:The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H(2)O(2))-induced damage. METHODS:Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min/day, 22 m/min, 6 degrees grade, 5 days/week). Isolated perfused working hearts from ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(03)00285-2
更新日期：2003-06-01 00:00:00
abstract：AIMS:Brugada syndrome (BrS) is an autosomal-inherited cardiac arrhythmia characterized by an ST-segment elevation in the right precordial leads of the electrocardiogram and an increased risk of syncope and sudden death. SCN5A, encoding the cardiac sodium channel Na(v)1.5, is the main gene involved in BrS. Despite the f...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvs211
更新日期：2012-10-01 00:00:00
abstract：:To define the interactions between blood and endocardium damaged by lactic acid, the left ventricles of 48 isolated continuously perfused and beating hearts were exposed for 0-4 hours to Krebs Henseleit buffer (KHB) with or without 33 mumol.ml-1 of lactic acid (pH 6.4). After excising its apex, the left ventricle was ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/23.6.478
更新日期：1989-06-01 00:00:00
abstract：OBJECTIVE:The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00447-9
更新日期：2002-09-01 00:00:00
abstract：:Inorganic nitrate from dietary and endogenous sources is emerging as a substrate for in vivo generation of nitric oxide (NO) and other reactive nitrogen oxides. Dietary amounts of nitrate clearly have robust NO-like effects in humans, including blood pressure reduction, inhibition of platelet aggregation, and vasoprot...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvq325
更新日期：2011-02-15 00:00:00
abstract：AIMS:Based on indirect methods, it has been suggested that both L- and T-type Ca(2+) channels mediate signalling in the renal afferent arteriole and that T-type Ca(2+) channels are involved in signalling in the efferent arteriole. However, Ca(2+) currents have never been studied in these two vessels. Our study was init...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvs310
更新日期：2013-02-01 00:00:00
abstract：OBJECTIVES:Anthracyclines cause apoptotic death in many cell types through activation of the ceramide pathway. We tested the hypothesis that doxorubicin induces cardiac myocyte apoptosis through ceramide generation. METHODS:Adult rat ventricular myocytes were grown in the presence of 10% fetal calf serum, and exposed ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(99)00142-x
更新日期：1999-08-01 00:00:00
abstract：OBJECTIVE:Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated g...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(97)00191-0
更新日期：1997-12-01 00:00:00
abstract：AIMS:Intracellular Ca(2+) ([Ca(2+)](i)) regulation in endothelial cells depends on transient receptor potential channels (TRPs), and the role of canonical TRPs (TRPCs) during hypoxia-reoxygenation (H-R) is unclear. We hypothesized that TRPC3 contributes to endothelial nitric oxide (NO) release and that H-R may reduce T...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr102
更新日期：2011-08-01 00:00:00
