Circulating Des-acyl Ghrelin Improves Cardiovascular Risk Prediction in Older Hypertensive Patients

Yano, Yuichiro; Nakazato, Masamitsu; Koji, Takehiko; Isobe, Takashi; Matsuda, Shuntaro; Hidaka, Toshiaki; Hayakawa, Manabu; Kangawa, Kenji; Shimada, Kazuyuki; Kario, Kazuomi

doi:10.1093/ajh/hpt232

Cited by 22 publications

(17 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, in mice cerebral circulation, des-acyl ghrelin but not ghrelin exerted protective effects through the modulation of NO release (21). Furthermore, in hypertensive patients, the plasma levels of des-acyl ghrelin were positively correlated to NO (22).…”

mentioning

confidence: 91%

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs

Grossini¹,

Raina²,

Farruggio³

et al. 2016

Endocrinology

View full text Add to dashboard Cite

Des-acyl ghrelin (DAG), the most abundant form of ghrelin in humans, has been found to reduce arterial blood pressure and prevent cardiac and endothelial cell apoptosis. Despite this, data regarding its direct effect on cardiac function and coronary blood flow, as well as the related involvement of autonomic nervous system and nitric oxide (NO), are scarce. We therefore examined these issues using both in vivo and in vitro studies. In 20 anesthetized pigs, intracoronary 100 pmol/mL DAG infusion with a constant heart rate and aortic blood pressure, increased coronary blood flow and NO release, whereas reducing coronary vascular resistances (P Ͻ .05). Dose responses to DAG were evaluated in five pigs. No effects on cardiac contractility/relaxation or myocardial oxygen consumption were observed. Moreover, whereas the blockade of muscarinic cholinoceptors (n ϭ 5) or ␣-and ␤-adrenoceptors (n ϭ 5 each) did not abolish the observed responses, NO synthase inhibition (n ϭ 5) prevented the effects of DAG on coronary blood flow and NO release. In coronary artery endothelial cells, DAG dose dependently increased NO release through cAMP signaling and ERK1/2, Akt, and p38 MAPK involvement as well as the phosphorylation of endothelial NO synthase. In conclusion, in anesthetized pigs, DAG primarily increased cardiac perfusion through the involvement of NO release. Moreover, the phosphorylation of ERK1/2 and Akt appears to play roles in eliciting the observed NO production in coronary artery endothelial cells. (Endocrinology 157: 2403-2415, 2016) T he ghrelin-related peptides, acylated ghrelin and desacylated ghrelin, are gastrointestinal hormones that have been reported to exert variable effects on the cardiovascular system. Apart from being able to stimulate food intake and adiposity (1-4), ghrelin has been found to reduce arterial and pulmonary blood pressure (BP) (5-8), to increase myocardial contractility (5, 9), and to exert opposite effects on different vascular beds (10 -13). For example, ghrelin has been shown to increase human forearm blood flow and dilate human mammary and rat mesenteric arteries, whereas in rats and pigs, it caused coronary vasoconstriction.The deacylated form of ghrelin, des-acyl ghrelin, is far more abundant in circulation than ghrelin and is devoid of any endocrine activity (1, 2, 4, 14), although several authors strongly suggest that des-acyl ghrelin has intrinsic and specific actions in many physiological and pathophysiological conditions, mainly as a functional antagonist of ghrelin (15). To date, however, the function of des-acyl ghrelin is currently unknown, with the few studies exam- Abbreviations: BP, blood pressure; CEC, coronary artery endothelial cell; DAG, des-acyl ghrelin; dP/dt max , maximum rate of change of LV systolic pressure; eNOS, endothelial NO synthase; GHSR, GH secretagogue receptor; LAD, left anterior descending coronary artery; L-NAME, N-nitro-L arginine methyl ester; LV, left ventricular; NO, nitric oxide; NOS, NO synthase; PKA, protein kinase A; PLC, phospholipase C; PO 2...

show abstract

mentioning

confidence: 91%

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs

Grossini¹,

Raina²,

Farruggio³

et al. 2016

Endocrinology

View full text Add to dashboard Cite

show abstract

“…It proved that ghrelin values declined with the increase in the number of cardiovascular risk factors in one individual, but only in case of male subjects; in females, the levels remained rather balanced [14]. A recent study demonstrated the possibility of using ghrelin as biomarker in cardiovascular events risk prognosis models [15].…”

Section: Discussionmentioning

confidence: 98%

“…However, ghrelin levels variations were not associated with the presence of any of the major cardiovascular risk factors. A recent study describes the possibility of using ghrelin as a biomarker for predicting the risk of CV events [15]. In order to justify the use of ghrelin in clinical practice, it is necessary to demonstrate an additional benefit in predicting cardiovascular risk.…”

Section: Discussionmentioning

confidence: 99%

Serum ghrelin level is associated with cardiovascular risk score

Pop

Peter

Dădârlat

et al. 2015

Romanian Journal of Internal Medicine

View full text Add to dashboard Cite

Ghrelin, a newly discovered bioactive peptide, was originally reported to induce growth hormone release. Recent studies have shown beneficial hemodynamic effects of ghrelin in the cardiovascular system to support the wide distribution of its receptors in cardiovascular tissues. The aim of the study was to determine whether cardiovascular risk factors influence plasma ghrelin levels.Methods. We evaluated in the Rehabilitation Hospital Cluj-Napoca, Cardiology -Department 88 consecutive subjects, 65 (73.86%) being women, with mean age 61.7±10.33 years. We assessed the presence of cardiovascular risk factors (obesity, arterial hypertension, diabetes mellitus, metabolic syndrome, smoking and lipid fractions). Plasma ghrelin levels were determined with a commercial ELISA kit (pg/ml).Results. After the evaluation of cardiovascular risk factors, we found no statistically significant difference between ghrelin levels in the patients with vs those without cardiovascular risk factors (p>0.05). A negative correlation was found between ghrelin levels and age, r = -0.32 (p <0.05). Using the HeartScore Internet tool we calculated the cardiovascular risk for each patient according to the risk score system (SCORE) for high cardiovascular risk countries. Statistically, the risk of fatal cardiovascular events in the next 10 years was indirectly correlated with the ghrelin levels in each patient -correlation between ghrelin levels and SCORE system r=-0.25, p=0.015. In conclusion, low serum ghrelin concentrations are associated with an increased global cardiovascular risk, calculated based on the European SCORE scale. However, we could not demonstrate a direct relationship between any of the major risk factors and ghrelin.

show abstract

“…Similar to AG, DAG can exert endothelial dependent and independent vasodilatory effects on human and rodent vasculature in vitro (15,24). In humans, lower levels of DAG are correlated with hypertension (25) and increased cardiovascular risk (26), but the direct effect of DAG on the human CV system has not been investigated prior to this study. Here, we compare the effects of AG and DAG infusions on BP and other autonomic parameters in healthy humans.…”

Section: Introductionmentioning

confidence: 99%

Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans

Zhang

Bidlingmaier

Altaye

et al. 2017

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective To compare the effects of acyl ghrelin (AG) and desacyl ghrelin (DAG) on blood pressure (BP), heart rate (HR), and other autonomic parameters in healthy humans and to elucidate hormonal mechanisms through which AG could exert cardiovascular (CV) effects. Design 17 healthy participants underwent frequent monitoring of systolic (sBP) and diastolic blood pressure (dBP), HR, respiratory rate (RR), and body surface temperature (Temp) during continuous infusion of AG, DAG, combined AG+DAG, or saline control before and during an IV-glucose tolerance test on 4 separate days. Plasma catecholamines, renin, and aldosterone levels were also measured. Differences in outcome measures between treatment groups were assessed using mixed model analysis. Results Compared to the saline control, AG and combined AG+DAG infusions decreased sBP, dBP, mean arterial blood pressure (MAP), HR, and Temp. In contrast, DAG infusion did not alter BP, RR, or Temp, but did decrease HR. The AG and AG+DAG infusions also raised plasma aldosterone levels compared to saline (p < 0.001) without affecting renin or catecholamine levels. Conclusions The decrease in BP, HR, RR, and Temp with AG infusion suggests mediation through the autonomic nervous system. The lack of response to DAG suggests that these autonomic effects require activation of the ghrelin receptor.

show abstract

Circulating Des-acyl Ghrelin Improves Cardiovascular Risk Prediction in Older Hypertensive Patients

Abstract: Des-acyl ghrelin improved the prediction of CVD events in older hypertensive patients.

Cited by 22 publications

References 30 publications

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs

Intracoronary Des-Acyl Ghrelin Acutely Increases Cardiac Perfusion Through a Nitric Oxide-Related Mechanism in Female Anesthetized Pigs

Serum ghrelin level is associated with cardiovascular risk score

Acute administration of acyl, but not desacyl ghrelin, decreases blood pressure in healthy humans

Contact Info

Product

Resources

About