Apelin protects myocardial injury induced by isoproterenol in rats

Jia, Yanjie; Pan, Chun‐Shui; Zhang, Jing; Geng, Bin; Zhao, Jing; Gerns, Helen; Yang, Jun; Chang, Jaw‐Kang; Tang, Chaoshu; Qi, Yongcheng

doi:10.1016/j.regpep.2005.09.033

Cited by 98 publications

(83 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 Szokodi et al 25 demonstrated that apelin was as effective a positive inotropic agent in the rat heart, 25 as ET-1, 44 and as adrenomedullin, 45 and we find that the apelins are the most potent endogenous agents in human atria reported so far. 40,46 Apelins have beneficial effects on cardiac performance in vivo in rats 24,26 and mice, 23 and the increase in the cardiac force of contraction in vitro that we observed suggests that apelin may also have this potential in humans. Positive inotropic effects in vivo may be mediated via reflex sympathetic activation.…”

Section: Discussionmentioning

confidence: 66%

“…22 We hypothesize that activation of smooth muscle APJ will produce vasoconstriction that is counterbalanced by dilatation, mediated by the endothelial APJ, 17 in a manner analogous to endothelin 1 (ET-1). 39 In the heart in vivo, apelin elicited inotropic actions in rodents [23][24][25][26] thought to result from reflex sympathetic activation. 27 However, inotropic effects in a rat-isolated heart 17,22 and localization of APJ in rat and human cardiomyocytes 17,22 suggested a direct action.…”

mentioning

confidence: 99%

See 1 more Smart Citation

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

et al. 2009

View full text Add to dashboard Cite

Abstract-Apelin receptors, present on vascular smooth muscle cells, endothelium, and cardiomyocytes, are activated by the family of apelin peptides to elicit cardiovascular effects in experimental animals, but functional activity in humans has not been studied in detail. We detected low levels of apelin immunoreactivity in plasma of volunteers consistent with an autocrine/paracrine action and detected apelin immunoreactivity in the supernatant from human cultured endothelial cells. We found that [Pyr 1 ]apelin-13 was the predominant isoform in cardiac tissue from patients with coronary artery disease. We tested the hypothesis that apelins have vascular and cardiac actions in human tissues in vitro and compared responses to [Pyr 1 ]apelin-13, apelin-13, and apelin-36. In endothelium-intact mammary artery, all 3 of the apelins induced concentration-dependent vasodilatation with comparable potency (EC 50 : 0.6 to 1.6 nM; maximum response: 40% to 50%). Vasodilatation was abolished after endothelial removal or preincubation with indomethacin but was unaffected by preincubation with N G -nitro-L-arginine methyl ester, indicating involvement of prostanoids but not NO in dilatation by apelins in this patient group. Apelins were potent constrictors of endothelium-denuded saphenous vein (EC 50 : 0.6 to 1.6 nM; maximum response: 17% to 26%) and mammary artery ([Pyr 1 ]apelin-13; EC 50 : 0.2 nM; maximum response: 29%). In paced atrial strips, all 3 of the peptides increased the force of contraction with subnanomolar potencies (EC 50 : 40 to 125 pM). For the first time, we demonstrate that the 3 principal forms of apelin have comparable potency and efficacy in human cardiovascular tissues. Apelins are potent endothelium-dependent vasodilators acting via a prostanoid-dependent mechanism; however, removal of the endothelium revealed direct vasoconstrictor actions in both the artery and vein. Furthermore, in human cardiac tissue, the apelin peptides are among the most potent endogenous positive inotropic agents yet reported. A pelin peptides, derived from a single gene, activate the G protein-coupled receptor APJ that has high sequence similarity with the angiotensin II type 1 receptor but does not bind angiotensin II. 1,2 The precursor, preproapelin, 2-4 contains several proteolytic cleavage sites, 3 predicting formation of C-terminal peptides, including apelin-36, apelin-13, and [Pyr 1 ]apelin-13, 2,3,5 but the endogenous isoforms in humans remain to be identified. APJ modulates fluid homeostasis 4 -6 and acts as coreceptor for HIV infection, 7,8 and apelin is a novel adipokine 9 -11 with an emerging role in the cardiovascular system. 6,12-38 A role for apelin in human cardiovascular disease has been proposed; importantly, mRNA microarray analysis of Ͼ12 000 genes identified APJ as the most consistently and significantly increased gene in heart failure patients after mechanical offloading. 12 Circulating levels of apelin may be unchanged 13 or raised 12 in early stages of heart failure but were normalized 12 or decreased...

show abstract

Section: Discussionmentioning

confidence: 66%

mentioning

confidence: 99%

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

et al. 2009

View full text Add to dashboard Cite

show abstract

“…Apelin has also been shown to exert cardioprotective effects, demonstrated against both I/R injury and isoproterenol-induced cardiotoxicity (Jia et al 2006, Kleinz & Baxter 2008. Administration of pharmacological doses of apelin (1 mM) reduced infarct size in both in vitro and in vivo murine I/R models, the in vitro effects being mediated via the RISK pathway .…”

Section: Apelinmentioning

confidence: 99%

Role of adipokines in cardiovascular disease

Mattu¹,

Randeva²

2012

Journal of Endocrinology

251

203

View full text Add to dashboard Cite

The discovery of leptin in 1994 sparked dramatic new interest in the study of white adipose tissue. It is now recognised to be a metabolically active endocrine organ, producing important chemical messengers -adipokines and cytokines (adipocytokines). The search for new adipocytokines or adipokines gained added fervour with the prospect of the reconciliation between cardiovascular diseases (CVDs), obesity and metabolic syndrome. The role these new chemical messengers play in inflammation, satiety, metabolism and cardiac function has paved the way for new research and theories examining the effects they have on (in this case) CVD. Adipokines are involved in a 'good-bad', yin-yang homoeostatic balance whereby there are substantial benefits: cardioprotection, promoting endothelial function, angiogenesis and reducing hypertension, atherosclerosis and inflammation. The flip side may show contrasting, detrimental effects in aggravating these cardiac parameters.

show abstract

“…Although the authors argued that this reduction might contribute to the contractile dysfunction, it may represent a protective limitation of the cardiac responsiveness to the inotropic effect of apelin. A decreased of apelin content in plasma, as well as in atrial and ventricular myocardium, may be obtained in rats with heart failure produced with repeated high doses of isoproterenol [88]. In this model, the heart failure is significantly improved by apelin administration.…”

Section: Apelin In Heart Failurementioning

confidence: 84%

Effects of apelin on the cardiovascular system

et al. 2015

View full text Add to dashboard Cite

Apelin is an endogenous peptide acting on the APJ receptor. It consists of several isoforms characterised by different numbers of aminoacids. The number of aminoacids in the active isoforms range from 36 to 12. Apelin-13 and, to a lesser extent, apelin-36 are considered the most active isoforms with the greatest activity on the cardiovascular homeostasis. The effects normally exerted by the basal level of endogenous apelin, can be enhanced not only by its up-regulation, but may also by its exogenous administration. The present review considers the effects of apelin on various aspects of the cardiovascular function, such as cardiac development, vasomotor tone, angiogenesis, myocardial inotropy in healthy and failing hearts as well as the prevention of ischemia-reperfusion injury, cardiac fibrosis and remodeling. Also the biphasic changes of apelin level during the evolution of heart failure are considered. Although the positive inotropic effect exerted by apelin in normal and failing hearts would suggest the use of this peptide in the treatment of heart failure, the limited duration and extent of its effect do not support this possibility, unless a long lasting (6 hours) infusion is performed to overcome the limit of its short life. However, although the data on the characteristics of the inotropic activity do not provide a strong support for the treatment of active heart failure, apelin may be used in the prevention of heart failure because of its activity in limiting the consequences of myocardial ischemia such as infarct size and cardiac remodeling. KeywordsApelin/APJ system, heart failure, ischemia-reperfusion injury, contractility, cardiac protection, Reninangiotensin system 2 The apelin/APJ system Apelin In 1998 Tatemoto et al. discovered the endogenous peptide capable of binding the G protein-coupled receptor (GPCR) APJ [1,2], which at that time was considered an orphan receptor becaue its ligand was unknown. The just discovered ligand was called, apelin e.g APj Endogenous LIgaNd. Apelin is expressed in hearts, lungs, kidneys, liver, adipose tissue, gastrointestinal tract, brain, adrenal glands, endothelium, and human plasma. The gene of apelin is located on chromosome X [3] and encodes a 77 aminoacid sequence called pre-pro-apelin [4]. Upon cleavage by a family of endopeptidases, pre-pro-apelin generates several C-terminal fragments of various size, which are classified on the basis of the number of aminoacids. The active isoforms range from 36 to 12 aminoacids. As fragments shorter than 12 aminoacids are biologically inactive, it appears evident that the Cterminal 12 aminoacids are essential for receptor binding, whereas the N-terminal sequence modulates the interaction with the receptor [5]. At present it is recognized that, although different isoforms display similar functions, active isoforms differ in tissue distribution, potency and receptor binding affinity [6]. Apelin-13 and, to a lesser extent, apelin-36 have been considered the most active isoforms with the greatest activity on the cardi...

show abstract

Apelin protects myocardial injury induced by isoproterenol in rats

Cited by 98 publications

References 20 publications

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

Role of adipokines in cardiovascular disease

Effects of apelin on the cardiovascular system

Contact Info

Product

Resources

About

Apelin protects myocardial injury induced by isoproterenol in rats

Cited by 98 publications

References 20 publications

[Pyr 1 ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

[Pyr 1 ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

Role of adipokines in cardiovascular disease

Effects of apelin on the cardiovascular system

Contact Info

Product

Resources

About

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart

[Pyr ¹ ]Apelin-13 Identified as the Predominant Apelin Isoform in the Human Heart