Cardiovascular Journal of Africa: Vol 28 No 3 (May/June 2017)

CARDIOVASCULAR JOURNAL OF AFRICA • Volume 28, No 3, May/June 2017

AFRICA

163

Hcy influences endothelial function, leading to a prothrombotic

environment, platelet activation, and endothelial leukocyte

interactions.

In addition, Hcy enhances inflammatory responses,

which are recognised for their role in atherosclerotic disease.

48,49

Recent studies

50,51

suggest that markers of inflammation may

reflect different aspects of the atherothrombotic process and

have a potential role in the prediction of risk for developing

coronary artery disease. Besides the detrimental effects of Hcy

on the cardiovascular system,

15,52

elevated Hcy levels are also

associated with peripheral arterial disease as well as venous

diseases such as deep-vein thrombosis.

Although there is strong evidence to suggest that increased

ghrelin levels lead to increased food intake and lipid deposition,

its cardiovascular benefits, such as the inhibition of cytokine

production and improved left ventricular function, have also been

well documented. Ghrelin receptors have been isolated in various

tissues, such as the endocrine glands and cardiovascular tissue.

In addition, receptor density changes have been demonstrated to

be an important part of the cardiovascular effects of ghrelin.

Targeting specific tissue receptors by modification of the ghrelin

molecule may achieve the desired cardiovascular effects without

activating the unwanted effects of ghrelin.

The mechanism of improvement in endothelial function

relates to improved eNOS expression and a reduction in oxidative

stress. Ghrelin also has a potent effect on blocking Hcy-induced

reduction in eNOS protein levels.

Disproportion in the quantity

of reactive oxygen species (ROS) generated during aerobic

metabolism is known to lead to oxidative stress and contribute

to vascular disease. This process is carried out through a variety

of mechanisms, including nitric oxide (NO) consumption and

depletion,

55,56

regulation of gene transcription,

and intracellular

alkalinisation.

Ghrelin reduced the production of superoxide

anion, a major type of ROS, in Hcy-treated porcine coronary

artery and human endothelial cell rings.

Conclusion

Serum Hcy, serum acylated ghrelin and saliva obestatin

levels were significantly elevated, while serum obestatin level

decreased in the IHD group. We believe that ghrelin is a potent

and effective protein that inhibits Hcy production and other

potentially damaging mechanisms and may underlie the decrease

in obestatin level, which counteracts ghrelin. It can also be

concluded from this study that saliva could be an alternative to

serum in the diagnosis and follow up of disease, but these results

should be confirmed with larger groups of subjects.

References

Gaziano T, Reddy KS, Paccaud F, Horton S, Chaturvedi V.

Cardiovascular disease. In: Jamison DT, Breman JG, Measham AR,

Alleyne G, Claeson M, Evans DB,

et al.

(eds).

Disease Control Priorities

in Developing Countries

. 2nd edn. Washington (DC): World Bank; 2006,

Ch 33: 645–662.

Farmer JA, Torre-Amione G. Atherosclerosis and inflammation.

Curr

Atheroscler Rep

2002;

: 92–98. PMID: 11822971.

Mason RP. Mechanisms of plaque stabilization for a charged calcium

channel blocker in coronary artery disease

. Pharmacotherapy

2001;

209–215. PMID: 11560191.

Ozbay Y, Aydin S, Dagli AF, Akbulut M, Dagli N, Kilic N,

et al

Obestatin is present in saliva: alterations in obestatin and ghrelin levels

of saliva and serum in ischemic heart disease.

BMB Rep

2008; 41: 55–61.

PMID: 18304451.

Kojima M, Kangawa K. Ghrelin, an orexigenic signaling molecule

from the gastrointestinal tract.

Curr Opin Pharmacol

2002;

: 665–668.

PMID: 12482728.

Tesauro M, Schinzari F, Caramanti M, Lauro R, Cardillo C. Metabolic

and cardiovascular effects of ghrelin.

Int J Pept

2010; 2010. pii: 864342.

doi: 10.1155/2010/864342.

Wu R, Dong W, Zhou M, Cui X, Hank Simms H, Wang P. Ghrelin

improves tissue perfusion in severe sepsis via downregulation of

endothelin-1.

Cardiovasc Res

2005;

: 318–326. PMID: 16018991.

Baldanzi G, Filigheddu N, Cutrupi S, Catapano F, Bonissoni S, Fubini

et al

. Ghrelin and des-acyl ghrelin inhibit cell death in cardiomyo-

cytes and endothelial cells through ERK1/2 and PI 3-kinase/AKT.

J Cell

Biol

2002;

159

: 1029–1037. PMID: 12486113.

Li A, Cheng G, Zhu GH, Tarnawski AS. Ghrelin stimulates angiogenesis

in human microvascular endothelial cells: Implications beyond GH release.

Biochem Biophys Res Commun

2007;

353

: 238–243. PMID: 17184731.

10. Iantorno M, Chen H, Kim JA, Tesauro M, Lauro D, Cardillo C,

et al

Ghrelin has novel vascular actions that mimic PI 3-kinase-dependent

actions of insulin to stimulate production of NO from endothelial cells.

Am J Physiol Endocrinol Metab

2007;

292

: 756–764. PMID: 17106060.

11. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL,

et al

Ghrelin inhibits proinflammatory responses and nuclear factor-

activation in human endothelial cells.

Circulation

2004;

109

: 2221–2226.

PMID: 15117840.

12. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K.

Ghrelin is a growth-hormone releasing acylated peptide from stomach.

Nature

1999;

402

: 656–660. PMID: 10604470.

13. Aydin, S. Discovery of ghrelin hormone: researches and clinical applica-

tions.

Turk J Biochem

2007;

: 76–89.

14. Petramala L, Acca M, Francucci CM, D’Erasmo E. Hyperhomo-

cysteinemia: a biochemical link between bone and cardiovascular system

diseases?

J Endocrinol Invest

2009;

: 10–14. PMID: 19724160.

15. Chen C, Conklin BS, Ren Z, Zhong D. Homocysteine decreases

endothelium-dependent vasorelaxation in porcine arteries.

J Surg Res

2002;

102

: 22–30. PMID:11792147.

16. Zhou W, Chai H, Lin PH, Lumsden AB, Yao Q, Chen C. Ginsenoside

Rb1 blocks homocysteine induced endothelial dysfunction in porcine

coronary arteries.

J Vasc Surg

2005;

: 861–868. PMID: 15886672.

17. Nagaya N, Moriya J, Yasumura Y, Uematsu M, Ono F, Shimizu W,

. Effects of ghrelin administration on left ventricular function, exer-

cise capacity, and muscle wasting in patients with chronic heart failure.

Circulation

2004;

110

: 3674–3679. PMID: 15569841.

18. Kalra DK. Homocysteine and cardiovascular disease.

Curr Atheroscler

Rep

2004;

: 101–106. PMID: 15023293.

19. Temple ME, Luzier AB, Kazierad DJ. Homocysteine as a risk factor for

atherosclerosis.

Ann Pharmacother

2000;

: 57–65. PMID: 10669187.

20. Kang SS, Wong PWK, Norusis M. Homocysteinemia due to folate defi-

ciency.

Metabolism

1987;

: 458–462. PMID: 3574134.

21. Krajcovicova-Kudlackova M, Blazicek P, Mislanova C, Valachovicova

M, Paukova V, Spustova V. Nutritional determinants of plasma homo-

cysteine.

Bratisl Lek Listy

2007;

108

: 510–515. PMID: 18309641.

22. Aydin S, Halifeoglu I, Ozercan IH, Erman F, Kilic N, Aydin S,

et al

. A

comparison of leptin and ghrelin levels in plasma and saliva of young

healthy subjects.

Peptides

2005;

: 647–652. PMID: 15752580.

23. Hosoda H, Doi K, Nagaya N, Okumura H, Nakagawa E, Enomoto M,

et al

. Optimum collection and storage conditions for ghrelin measure-

ments: octanoyl modification of ghrelin is rapidly hydrolyzed to deacyl