Cardioprotective Effect of Ghrelin in Cardiopulmonary Bypass Involves a Reduction in Inflammatory Response

Abstract

BackgroundGhrelin has been reported to protect the cardiovascular system; however, the cardioprotective effect of ghrelin against cardiopulmonary bypass (CPB) induced myocardial injury are unclear. In this study, the protective effect of ghrelin on CPB induced myocardial injury and the underlying mechanisms were investigated.Methods and ResultsAdult male rats were subjected to CPB and randomly to receive vehicle (n = 8), ghrelin (n = 8), ghrelin plus [D-Lys3]-GHRP-6, a GHSR-1a inhibitor (n = 8), or ghrelin plus wortmannin, a phosphoinositide 3′-kinase (PI3K) inhibitor (n = 8). In vitro study was performed on cultured cardiomyocytes subjected to simulated cardiopulmonary bypass (SCPB). Ghrelin attenuated the inflammatory response, as evidenced by reduced induction of TNF-α, IL-6 and myocardial myeloperoxidase activity and concurrent reduction in apoptosis, oxidative stress, and levels of myocardial injury markers following CPB. Moreover, ghrelin significantly increased cardiac function after CPB. In cultured cardiomyocytes subjected to simulated CPB, ghrelin increased cell viability and decreased the percentage of apoptotic myocytes. Inhibition of ghrelin downstream signaling blocked the cardioprotective effects both in vivo and vitro.ConclusionsGhrelin could provide an effective approach to the attenuation of CPB induced myocardial injury. The cardioprotective effects elicited by ghrelin may contribute to the inhibition of inflammatory response through the Akt-activated pathway.

Ghrelin: Ghrelin as a Regulatory Peptide in Growth Hormone Secretion

“…However, the morphological characteristics and thorough distribution of ghrelin cells in the gastrointestinal tract has not been defined. Ghrelin is also produced in small amounts by other organs like heart, lung, lymphatic tissue, kidney, adrenal glands, thyroid gland, pancreas, gonads, some neoplastic tissues and cancer-cell lines [15][16][17]. Ghrelin-immunoreactive neurons are present in few regions of the brain like the arcuate and the ventromedial nucleus of the hypothalamus, cerebellum and brainstem [12,[18][19][20].…”

Ghrelin gene products, receptors, and GOAT enzyme: biological and pathophysiological insight

“…Similarly, AG treatment reduces inflammatory response, apoptosis and oxidative stress, and preserves the cardiac pumping function in a rat model of cardiopulmonary bypass through GHSR1a and Akt signaling (Cao et al 2013). In addition, AG exerts a protective effect against ischemia/reperfusion injury (Chang et al 2004), probably through a direct effect on the heart (Kishimoto et al 2012) and also exerts a vasodilatory effect in the vasculature (Isgaard & Granata 2011, Lacerda-Miranda et al 2012, which may be of potential importance for the development of atherosclerosis.…”

Ghrelin

“…A recent study in a rat model of cardiopulmonary bypass (CPB) shows that ghrelin treatment reduces inflammatory responses, apoptosis and oxidative stress induced by CPB, and preserves the cardiac pumping function through GHS-R1a and Akt signaling (15). Increased angiogenesis is measured by changes in vascular endothelial growth factor (VEGF), VEGF receptor, and nitric oxide (NO) (45).…”