Levosimendan improves LV systolic and diastolic performance at rest and during exercise after heart failure

The new myofilament Ca2+ sensitizer levosimendan (LSM) is a positive inotropic and vasodilatory agent. Its beneficial effects have been demonstrated at rest in congestive heart failure (CHF). However, its effect during exercise (Ex) in CHF is unknown. We assessed the effects of LSM on left ventricular (LV) dynamics at rest and during Ex in eight conscious, instrumented dogs with pacing-induced CHF. After CHF, with dogs at rest, LSM decreased arterial elastance (Ea) and increased LV contractile performance as assessed by the slope of LV pressure-volume (P-V) relation. LSM caused a >60% increase in the peak rate of mitral flow (dV/dtmax) due to decreases in minimal LV pressure and the time constant of LV relaxation (tau). LV arterial coupling, quantified as the ratio of end-systolic elastance (Ees) to Ea, was increased from 0.47 to 0.85%. LV mechanical efficiency, determined as the ratio of stroke work to total P-V area, was improved from 0.54 +/- 0.09 to 0.61 +/- 0.07. These beneficial effects persisted during Ex after CHF. Compared with CHF Ex dogs, treatment with LSM prevented Ex-induced abnormal increases in mean left atrial pressure and end-diastolic pressure and decreased Ees/Ea. With LSM treatment during CHF Ex, the early diastolic portion of the LV P-V loop was shifted downward with decreased minimal LV pressure and tau values and a further augmented dV/dtmax. Ees/Ea improved, and mechanical efficiency further increased from 0.61 +/- 0.07 to 0.67 +/- 0.07, which was close to the value reached during normal Ex. After CHF, LSM produced arterial vasodilatation; improved LV relaxation and diastolic filling; increased contractility, LV arterial coupling, and mechanical efficiency; and normalized the response to Ex.     

A diastolic dysfunction model in non-human primates with transverse aortic constriction

Transverse aortic constriction (TAC) has been widely used to study cardiac hypertrophy, fibrosis, diastolic dysfunction, and heart failure in rodents. Few studies have been reported in preclinical animal models. The similar physiology and anatomy between non-human primates (NHPs) and humans make NHPs valuable models for disease modeling and testing of drugs and devices. In the current study, we aimed to establish a TAC model in NHPs and characterize the structural and functional profiles of the heart after TAC. A non-absorbable suture was placed around the aorta between the brachiocephalic artery and left common carotid artery to create TAC. NHPs were divided into 2 groups according to pressure gradient (PG): the Mild Group (PG=31.01 ± 12.40 mmHg, n=3) and the Moderate Group (PG=53.00 ± 9.37 mmHg, n=4). At 4 weeks after TAC, animals in both TAC groups developed cardiac hypertrophy: enlarged myocytes and increased wall thickness of the left ventricular (LV) anterior wall. Although both TAC groups had normal systolic function that was similar to a Sham Group, the Moderate Group showed diastolic dysfunction that was associated with more severe cardiac fibrosis, as evidenced by a reduced A wave velocity, large E wave velocity/A wave velocity ratio, and short isovolumic relaxation time corrected by heart rate. Furthermore, no LV arrhythmia was observed in either animal group after TAC. A diastolic dysfunction model with cardiac hypertrophy and fibrosis was successfully developed in NHPs.     

Role of cardiac renin-angiotensin system in the development of pressure-overload left ventricular hypertrophy in rats with abdominal aortic constriction

Possible involvement of cardiac renin-angiotensin system (RAS) in pressure overload induced left ventricular hypertrophy (LVH) was investigated. Rats were subjected to abdominal aortic constriction (AAC) and examined the effects of 4 weeks treatments with an angiotensin converting enzyme (ACE) inhibitor, captopril and a vasodilator, hydralazine on haemodynamics and ventricular RNA, DNA, protein and myosin isoform pattern in sham and hypertrophied rats. AAC increased the mean arterial pressure (MAP) and systolic blood pressure (SBP), and resulted in increased left ventricle/body weight ratio, LV thickness, RNA and protein content, however total DNA was not changed. The expression of fetal isogene, -myosin heavy chain (-MHC), was markedly enhanced where as u.-MHC was reduced. High-dose captopril (100 mg/kg p.o.,) significantly prevented the increase in haemodynamics, development of LVH, LV remodeling, increase in total protein, RNA and antithetical expression of myosin isoforms. Hydralazine (15 mg/kg p.o.,), did not modulate hypertrophic changes and low-dose captopril (1.5 mg/kg p.o.,) which has not produced any marked fall in MAP and SBP also modulated favourably the development of LVH and its biochemical markers. Thus, the prevention of the development of LVH and induction of -MHC by non-hypotensive doses of captopril may be related to the blockade of intracardiac production of angiotensin II rather than circulating system. These results suggest that cardiac RAS may play an important role in pressure overload induced LVH.     

主动脉弓缩窄诱导大鼠心肌肥大Raf/MEK/ERK通路的变化

目的:通过观察心肌肥大大鼠加速纤维肉瘤/丝裂素活化蛋白激酶激酶/胞外信号调节蛋白激酶(Raf/MEK/ERK)通路关键因子的基因和蛋白表达及蛋白磷酸化修饰水平上的变化,了解Raf/MEK/ERK通路在心肌肥大调控中的作用。方法: 20只SD大鼠随机分为假手术组和模型组,通过主动脉弓缩窄(TAC)法建立心肌肥大模型,12周后颌下静脉取血分离血清,检测氨基末端脑钠肽前体(NT-proBNP)含量,之后进行超声心动图测定和麻醉下的血流动力学测定,收集心肌标本,观察心肌组织的病理学改变,检测心肌组织Raf/MEK/ERK通路的关键因子基因、蛋白表达水平及蛋白磷酸化水平的变化。结果:与假手术组比较,TAC模型组大鼠超声心动图的左室舒张末期室间隔厚度(IVSd)、左室收缩末期室间隔厚度(IVSs)、左室后壁舒张末期厚度(LVPWd)、左室后壁收缩末期厚度(LVPWs)显著增厚(P＜0.05,P＜0.01),左室收缩末期内径(LVIDs)显著减小(P＜0.01),左心室质量(LV Mass)、左心系数LW(LV Mass/Weight)比值显著增加(P＜0.05,P＜0.01);大鼠心率(HR)、左心室最大收缩速率(+dp/dtmax)、左心室最大舒张速率(-dp/dtmax) 均显著降低(P＜0.01),血清中NT-pro BNP含量显著增加(P＜ 0.01);心肌细胞排列杂乱,心肌细胞肥大、胞质明显增多,炎症细胞浸润,出现大量胶原纤维沉积,大面积心肌细胞呈现蓝色;大鼠心肌组织中c-Raf在Ser259和Ser338上的磷酸化蛋白phospho-c-Raf (Ser259)和phospho-c-Raf (Ser338) 表达水平显著升高(P＜0.01),其下游MEK1/2、ERK1/2的磷酸化蛋白phospho-MEK1/2(Ser217/Ser221)和phospho-ERK1/2 (Thr202/Tyr204)表达水平也显著增高(P＜0.01)。结论: Raf/MEK/ERK通路在心肌肥大中的调控作用,可能通过激活关键因子c-Raf、MEK1、MEK2、ERK1和ERK2特异性位点的磷酸化实现的。     

腹主动脉缩窄小鼠心脏结构和功能的动态变化*

目的: 探讨腹主动脉缩窄小鼠在向心衰发展的过程中心脏结构和功能的动态变化。方法: 健康雄性昆明小鼠,随机分为模型组、假手术组和对照组。模型组采用腹主动脉缩窄的方法制备慢性心力衰竭小鼠模型,假手术组只分离出腹主动脉但不结扎,对照组不做任何处理。模型组组内分为2周组、4周组、6周组和8周组,每组10只。观察各组小鼠行为学表现、心电图、超声心动图和心肌组织病理学的变化。结果: 模型组与对照组相比:模型组小鼠术后2周开始出现行为学改变并且仅有2周组小鼠出现IVSS降低(P＜0.05);术后4周开始出现病理性J波、EF降低(P＜0.05)、IVSD增加(P＜0.05)和心肌损伤;术后6周开始出现LVPWD和LVPWS增加(P＜0.05);术后8周开始出现LV mass corrected增加(P＜0.05)。各组小鼠心率、R幅值、T幅值、ST段、PR间期、QT间期、QTc等数据差异均无显著性。结论: 腹主动脉缩窄导致小鼠出现心衰的过程中出现了EF降低、室间隔肥厚、病理性J波、左室后壁肥厚以及左室质量增加等变化。     

Echocardiographic assessment of LV hypertrophy and function in aortic-banded mice: necropsy validation

We characterized the time course of the left ventricular (LV) geometric and functional changes after aortic banding, validated them by necropsy, and investigated the sensitivity of echocardiographic findings on LV hypertrophy. C57BL/6 mice were subjected to transverse aortic constriction (TAC) or sham operation; echocardiographic assessments were performed before or at 2, 4, 6, and 11 wk after surgery; and some of the mice were euthanized at the corresponding time points. There was a progressive increase in diastolic posterior wall thickness and LV systolic dimension; the percentage of LV fractional shortening (LV%FS) decreased progressively at 4 wk, whereas these parameters remained stable in sham-operated mice. Echo LV mass and LV%FS correlated well with actual whole heart mass and ratio of lung weight to body weight, respectively (r = 0.765 and -0.749, respectively; P < 0.0001). These results suggest that the development of myocardial hypertrophy and systolic dysfunction is a time-dependent process. Echocardiographic assessment of myocardial hypertrophy and functional changes correlate well with the actual heart mass and lung mass. Echocardiography is sensitive enough to assess myocardial hypertrophy and heart functional changes induced by pressure overload in mice.     

主动脉缩窄术模型小鼠成模早期评价技术

目的利用超声多普勒技术分析建立主动脉缩窄小鼠模型早期评价方法。方法 C57BL/6J小鼠经开胸手术结扎主动脉弓,获得理论直径为0.4 mm的无名动脉远端主动脉弓重建血管;超声多普勒分析重建小鼠主动脉弓及其分支内血流流速,分析小鼠主动脉重建情况;记录小鼠生存情况,Spss16.0软件Kaplan-Meier curves分析小鼠存活率;将术后1周多普勒血流分析数据与术后4周左室壁厚度做相关性分析;生物信息学总结分析国内外立该模型的技术与评价,综合分析建立主动脉缩窄小鼠模型的超声多普勒早期评价方法,为相关研究者提供参考。结果术后8周时重建组(TAC)小鼠存活率为85.0%(n=40),而假手术组(Sham)小鼠存活率为96.4%(n=28);小鼠术后1周超声多普勒检测无名动脉血流/左颈总动脉血流比值(IA/LCCA)大于5.9时,术后4周舒张期左室后壁厚度(LVPWD)显著增厚占比达100%;IA/LCCA于5.9～10.7之间时与LVPWD成线性相关,当IA/LCCA大于10.7时线性关系下降,LVPWD增大趋势变缓。结论 TAC小鼠术后1周时使用多普勒血流分析,IA/LCCA比值大于5.9时,术后4周小鼠LVPWD即发生显著增厚,超声多普勒血流分析可以作为模型是否成功的早期评价方法。     

Chronic doxycycline exposure accelerates left ventricular hypertrophy and progression to heart failure in mice after thoracic aorta constriction

Tetracycline is a powerful tool for controlling the expression of specific transgenes (TGs) in various tissues, including heart. In these mouse systems, TG expression is repressed/enhanced by adding doxycycline (Dox) to the diet. However, Dox has been shown to attenuate matrix metalloproteinase (MMP) expression and activity in various tissues, and MMP inactivation mitigates left ventricular (LV) remodeling in animal models of heart failure. Therefore, we examined the influence of Dox on LV remodeling and MMP expression in mice after transverse aortic constriction (TAC). One month after TAC, cardiac hypertrophy (99% vs. 67%) and the proportion of mice exhibiting congestive heart failure (CHF, 74% vs. 32%) were higher in the TAC + Dox group than in the TAC group (P < 0.05). These differences were no longer seen 2 mo after TAC, although LV was more severely dilated in TAC + Dox mice than in TAC mice (P < 0.05). One month after TAC, the increase in brain natriuretic peptide and beta-myosin heavy chain mRNA levels was 1.6 and 1.7 times higher, respectively, in TAC + Dox mice than in TAC mice (P < 0.01). MMP-2 gelatin zymographic activity increased 1.9- and 2.4-fold in TAC and TAC + Dox mice, respectively (P < 0.01 and P < 0.05 relative to respective sham-operated animals), but the difference between TAC + Dox and TAC mice did not reach statistical significance. Dox did not significantly alter TAC-associated perivascular and interstitial myocardial fibrosis. These findings demonstrate that Dox accelerates the onset of cardiac hypertrophy and the progression to CHF following TAC in mice. Accordingly, care should be taken when designing and interpreting studies based on TG mouse models of LV hypertrophy using the tetracycline-regulated (tet)-on/tet-off system.     

Cardiac hypertrophy in rats after supravalvular aortic constriction. I. Size and number of cardiomyocytes, endothelial and interstitial cells

The ascending aorta of 22 adult male Sprague-Dawley rats was constricted with a silver ring, and 25 animals were subjected to a sham-operation. The hearts, including the main arteries, were fixed by retrograde perfusion 3, 7, 14, 21 and 35 days after the operation. The cross-sectional area of the aorta was reduced by the constriction to an average of 20% of the values found after sham-operation. Twenty-one days after the constriction the weight of the left ventricular myocardium including the septum was increased 1.7-fold compared with controls. No further increase in weight was observed 35 days after the operation. The relative volumes of the tissue components remained largely constant in the subepicardial myocardium. In the subendocardial myocardium, however, the volume fraction of interstitial and, to a lesser extent, of endothelial tissue was significantly increased. Twenty-one days after constriction the estimated total volumes of the different myocardial components per left ventricle were increased 1.7-fold for heart muscle parenchyma, 1.8-fold for endothelial tissue, 2.9-fold for interstitial tissue, and 1.3-fold for capillary lumina compared with controls. At 35 days, only the interstitial tissue showed a further increase to 4.8-fold of control values. The mean cardiomyocyte volume was increased after aortic constriction in proportion to the increase in left ventricular weight, i.e. 1.7-fold over controls at 21 days. After 35 days its value was 29,500 +/- 790 micron 3 in rats subjected to aortic constriction compared with 16,800 +/- 640 micron 3 in controls. At this time the estimated number of cardiomyocytes per left ventricle showed no significant differences between experimental animals (2.9 X 10(7)) and controls (3.1 X 10(7)). Endothelial and interstitial cells were not only increased in average single cell volume (1.3-fold and 2.0-fold, respectively), but also in number per left ventricle (1.4-fold and 2.7-fold, respectively). Two-dimensional parameters indicated that during hypertrophy the capillary supply lagged behind the overall mass increase but achieved control levels on termination of hypertrophic growth at 35 days. These results show that even in pronounced hypertrophy the increase in mass of the myocardial parenchyma in the rat is due exclusively to an enlargement of cardiomyocytes (hypertrophy), whereas in endothelial and interstitial tissues enlargement of cells as well as increase in cell number (hyperplasia) also plays a role.     

Calcium channels and cation transport ATPases in cardiac hypertrophy induced by aortic constriction in newborn rats

In order to evaluate the contribution of pinocytosis to basal (no agonist) and lanthanide-insensitive store-activated Ca²⁺ inflow in freshly-isolated rat hepatocytes, the uptake of extracellular fluid by pinocytosis was measured at 20°C and used to predict the amount of extracellular Ca²⁺ taken up by pinocytosis. This was compared with the measured rate of Ca²⁺ uptake in the basal state, and with the measured lanthanide-insensitive component of divalent cation uptake stimulated by 2,5-di-tert-butylhydroquinone (DBHQ), an inhibitor of the smooth endoplasmic reticulum (Ca²⁺ + Mg²⁺)ATP-ase. Fluid uptake by pinocytosis was measured using [¹⁴C]sucrose. In hepatocytes incubated at 20°C, DBHQ increased the initial rate of sucrose uptake by about 35%. The data for sucrose uptake were used to calculate the volume of extracellular fluid taken up by pinocytosis which, in turn, was used to predict the amount of extracellular Ca ²⁺ taken up through pinocytosis in the basal and DBHQ-stimulated states. Rates of divalent cation inflow in the basal state were determined at 20°C by measuring the uptake of ⁴⁵Ca²⁺. The degree of stimulation of Ca²⁺ inflow by DBHQ and the lanthanide-insensitive component of DBHQ-stimulated divalent cation inflow were determined by measuring the rate of Mn²⁺-induced quenching of intracellular quin-2 in the absence of an agonist, and in the presence of DBHQ or DBHQ plus Gd³⁺. It was calculated that the process of pinocytosis accounts for at least 15% of Ca²⁺ uptake in the basal (no agonist) state, and for about 10% of DBHQ-stimulated lanthanide-insensitive Ca²⁺ uptake. It is concluded that in isolated hepatocytes (i) the release of Ca²⁺ from intracellular stores stimulates pinocytosis and (ii) the process of pinocytosis can account for a substantial proportion of basal Ca²⁺ inflow and a small proportion of DBHQ-stimulated lanthanide-insensitive Ca²⁺ inflow.Abbreviations RACC receptor-activated Ca²⁺ channel - DBHQ 2,5-di-tert-butylhydroquinone - [Ca²⁺] intracellular free Ca²⁺ concentration     

Pressure overload-induced LV hypertrophy and dysfunction in mice are exacerbated by congenital NOS3 deficiency

To investigate the role of endothelial nitric oxide synthase (NOS3) in left ventricular (LV) remodeling induced by chronic pressure overload, the impact of transverse aortic constriction (TAC) on LV structure and function was compared in wild-type (WT) and NOS3-deficient (NOS3(-/-)) mice. Before TAC, LV wall thickness, mass, and fractional shortening were similar in the two mouse strains. Twenty-eight days after TAC, both WT and NOS3(-/-) mice had increased LV wall thickness and mass as well as decreased fractional shortening. Although the pressure gradient across the TAC was similar in both strains of mice 28 days after TAC, LV mass and posterior wall thickness were greater in NOS3(-/-) than in WT mice, whereas fractional shortening and the maximum rate of developed LV pressure were less. Diastolic function, as measured by the time constant of isovolumic relaxation and the maximum rate of LV pressure decay, was impaired to a greater extent in NOS3(-/-) than in WT mice. The degree of myocyte hypertrophy and LV fibrosis was greater in NOS3(-/-) than in WT mice at 28 days after TAC. Mortality was greater in NOS3(-/-) than in WT mice 28 days after TAC. Long-term administration of hydralazine normalized the blood pressure and prevented the LV dilation in NOS3(-/-) mice but did not prevent the LV hypertrophy, dysfunction, and fibrosis associated with NOS3 deficiency after TAC. These results suggest that the absence of NOS3 augments LV dysfunction and remodeling in a murine model of chronic pressure overload.     

The protective effect of isosteviol sodium on cardiac function and myocardial remodelling in transverse aortic constriction rat

Pathological hypertrophy contributes to heart failure and there is not quite effective treatment to invert this process. Isosteviol has been shown to protect the heart against ischaemia-reperfusion injury and isoproterenol-induced cardiac hypertrophy, but its effect on pressure overload-induced cardiac hypertrophy is still unknown. Pressure overload induced by transverse aortic constriction (TAC) causes cardiac hypertrophy in rats to mimic the pathological condition in human. This study examined the effects of isosteviol sodium (STVNa) on cardiac hypertrophy by the TAC model and cellular assays in vitro. Cardiac function test, electrocardiogram analysis and histological analysis were conducted. The effects of STVNa on calcium transient of the adult rat ventricular cells and the proliferation of neonatal rat cardiac fibroblasts were also studied in vitro. Cardiac hypertrophy was observed after 3-week TAC while the extensive cardiac dysfunction and electronic remodelling were observed after 9-week TAC. Both STVNa and sildenafil (positive drug) treatment reversed the two process, but STVNa appeared to be more superior in some aspects and did not change calcium transient considerably. STVNa also reversed TAC-induced cardiac fibrosis in vivo and TGF-β1-induced fibroblast proliferation in vitro. Moreover, STVNa, but not sildenafil, reversed impairment of the autonomic nervous system induced by 9-week TAC.     

Relationship between hypertension, hypertrophy, and opening angle of zero-stress state of arteries following aortic constriction

Examination of changes occurring in the zero-stress state of an organ provides a way to study cellular growth in the organ due to change of physical stresses. The zero-stress state of the aorta is not a tube. It is a sector with an opening angle that varies with the location on the aorta and changes with cellular remodeling. Blood vessel remodeling can be induced by imposing a constriction on the abdominal aorta by a metal clip (aortic banding), which causes an increase of blood pressure, hypertrophy of the aortic wall, and large change of opening angle. The correlation of the opening angle with the blood vessel wall thickness and blood pressure changes in rat's aorta due to aortic banding is presented in this report. The opening angle changes daily following the aortic banding. Blood pressure rises in vessels of the upper body, but that in the lower body decreases at first and then rises to an asymptotic value. Blood vessel wall thickness increases in rough proportion to blood pressure. Vessel diameter changes also. But the most dramatic is the course of change of the zero-stress state. Typically, the time to reach 50 percent of asymptotic hypertrophy of blood vessel wall thickness is about 3-5 days. The corresponding time for blood pressure is about 7 days. The opening angle of the zero-stress state, however, increases rapidly at first, reaches a peak in about 2 to 4 days, then decreases gradually to a reduced asymptote. The exact values of the time constants depend on the location along the aortic tree. In general, the course of change of residual strain is very different from those of the blood pressure and the blood vessel wall thickness.     

Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice

Recent studies have been directed at modulating the heart failure process through inhibition of activated matrix metalloproteinases (MMPs). We hypothesized that a loss of MMP inhibitory control by tissue inhibitor of MMP (TIMP)-1 deficiency alters the course of postinfarction chamber remodeling and induced chronic myocardial infarction (MI) in wild-type (WT) and TIMP-1(-/-) mice. Left ventricular (LV) pressure-volume loops obtained from WT and TIMP-1(-/-) mice demonstrated that LV end-diastolic volume [52 +/- 4 (WT) vs. 71 +/- 6 (TIMP-1(-/-)) microl] and LV end-diastolic pressure [9.0 +/- 1.2 (WT) vs. 12.7 +/- 1.4 (TIMP-1(-/-)) mmHg] were significantly increased in the TIMP-1(-/-) mice 2 wk after MI. LV contractility was reduced to a similar degree in the WT and TIMP-1(-/-) groups after MI, as indicated by a significant fall in the LV end-systolic pressure-volume relationship. Ventricular weight and cross-sectional areas of LV myocytes were significantly increased in TIMP-1(-/-) mice, indicating that the hypertrophic response was more pronounced. The observed significant loss of fibrillar collagen in the TIMP-1(-/-) controls may have been an important contributory factor for the observed LV alterations in the TIMP-1(-/-) mice after MI. These findings demonstrate that TIMP-1 deficiency amplifies adverse LV remodeling after MI in mice and emphasizes the importance of local endogenous control of cardiac MMP activity by TIMP-1.     

Sympathetic innervation of blood vessels in rats with aortic constriction hypertension

The adrenergic innervation of blood vessel wall was studied in various vascular beds of adult rats with experimental hypertension induced by the constriction of the aorta between the origins of both renal arteries. A moderate expansion of body fluids was demonstrated in this hypertensive model. The decrease of the density of adrenergic plexus in the vessel wall as well as the diminished catecholamine fluorescence were found only in renal vessels. These changes were pronounced in the left renal artery and vein even if the left kidney was not subjected to elevated blood pressure. Thus the alteration of vascular adrenergic innervation in hypertensive rats is not a consequence of high blood pressure but it seems to be a part of neurohumoral pathogenetic mechanisms.     

Erythropoietin improves operant conditioning and stability of cognitive performance in mice

Background  

Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion.     

Visfatin aggravates transverse aortic constriction-induced cardiac remodelling by enhancing macrophage-mediated oxidative stress in mice

Previous studies have reported that visfatin can regulate macrophage polarisation, which has been demonstrated to participate in cardiac remodelling. The aims of this study were to investigate whether visfatin participates in transverse aortic constriction (TAC)-induced cardiac remodelling by regulating macrophage polarisation. First, TAC surgery and angiotensin II (Ang II) infusion were used to establish a mouse cardiac remodelling model, visfatin expression was measured, and the results showed that TAC surgery or Ang II infusion increased visfatin expression in the serum and heart in mice, and phenylephrine or hydrogen peroxide promoted the release of visfatin from macrophages in vitro. All these effects were dose-dependently reduced by superoxide dismutase. Second, visfatin was administered to TAC mice to observe the effects of visfatin on cardiac remodelling. We found that visfatin increased the cross-sectional area of cardiomyocytes, aggravated cardiac fibrosis, exacerbated cardiac dysfunction, further regulated macrophage polarisation and aggravated oxidative stress in TAC mice. Finally, macrophages were depleted in TAC mice to investigate whether macrophages mediate the regulatory effect of visfatin on cardiac remodelling, and the results showed that the aggravating effects of visfatin on oxidative stress and cardiac remodelling were abrogated. Our study suggests that visfatin enhances cardiac remodelling by promoting macrophage polarisation and enhancing oxidative stress. Visfatin may be a potential target for the prevention and treatment of clinical cardiac remodelling.