Ghrelin reduces rat myocardial calcification induced by nicotine and vitamin D3 in vivo

Abstract

Abstract. Ghrelin, a newly discovered bioactive peptide, initially was identified as a strong stimulant for the release of growth hormone (GH) and that has improved cardiac function in patients suffering from end-stage chronic heart failure. Increasing evidence has demonstrated that ghrelin may have myocardial protective effects. However, the role of ghrelin in the pathogenesis of cardiovascular diseases remains unclear. In this study, an in vivo model of rat myocardial calcification induced by vitamin D3 and nicotine was used to study the possible mechanism in the regulatory action of ghrelin on the calcified myocardium. Calcification increased total Ca 2+ content and 45 Ca 2+ deposition in the myocardium and alkaline phosphatase (ALP) activation in the plasma. Compared with the control group, ghrelin mRNA expression was up-regulated and the myocardium calcium content was significantly increased in vitamin D3 and nicotine-treated rats. Rats were subcutaneously injected with 1 or 10 nmol/kg ghrelin. Rats treated with both low-and high-dose ghrelin decreased total Ca 2+ content and 45 Ca 2+ deposition in cardiac muscle and inhibited ALP activation in the myocardium and plasma, in a concentration-dependent manner. In addition, osteopontin (OPN) mRNA expression significantly decreased and that of endothelin (ET-1) significantly increased with myocardial calcification. Ghrelin treatment increased OPN expression at the mRNA level and reduced ET-1 mRNA expression in a dose-dependent manner. These results indicate that exogenous administration with ghrelin attenuates myocardial calcification induced by nicotine and vitamin D3, and that the possible mechanism is via the ghrelin-induced increase in the OPN mRNA levels and decrease in the ET-1 mRNA expression in the myocardium.

Increased ghrelin signaling prolongs survival in mouse models of human aging through activation of sirtuin1

“…Ghrelin was reported to attenuate myocardial calcification induced by nicotine and vitamin D3 via an increase and decrease in osteopontin and endothelin-1 expression, respectively, in the myocardium. 53 The mechanism through which leukemia, the main cause of death in SAMP8 mice, was inhibited by treatment with rikkunshito remains clarified in relation to ghrelin.…”

Ghrelin hormone might have a potential role in amelogenesis

“…2,[25][26][27]33,38,39 Multifunctional hormone Ghrelin directly regulates bone development in relation to these proteins. 22,[28][29][30][40][41][42] Odontogenesis occurs as a result of sequential and reciprocal interactions between the oral ectoderm and the neural crest-derived mesenchyme. Tooth crown development morphologically starts with the thickening of the epithelium and progresses through bud, cap and bell forms creating by this thickened epithelium.…”

“…It is noteworthy to point out here; interestingly, Ghrelin enhances the expression of osteoblastic genes in the bone while reducing vascular calcification despite both tissues developing through the same mechanisms. 22,23,[28][29][30][31][32][40][41][42][55][56][57][58][59][60] It has been reported that osteoblastic differentiation and calcification of vascular smooth muscle cells are inhibited by administering high doses of Ghrelin but not at low Ghrelin levels. 30 On the contrary, Maccarinelli et al 32 reported that although…”

“…2 , 25-27 Ghrelin is involved in bone mineralisation and vascular calcification as a regulator by influencing the GH/Insulin-like growth factor-1(IGF-1) axis, bone alkaline phosphatase (BALP), osteocalcin (OC), runt-related transcription factor 2 (Runx2), bone morphogenetic protein-2 (BMP-2) and extracellular signal-regulated kinase (ERK) signalling pathway. 22,[28][29][30][31][32] These factors are known to play a role in the development of the dental hard tissues. 5,6,25,27,33,34 It may be assumed that possible deviations in Ghrelin hormone levels could be attributed to the consequences mentioned above.…”