Sites of action of ghrelin receptor ligands in cardiovascular control

Callaghan, Brid; Hunne, Billie; Hirayama, Haruko; Sartor, Daniela M.; Nguyen, Trung Van; Abogadie, Fe C.; Ferens, Dorota; McIntyre, Peter; Ban, Kanako; Baell, Jonathan B.; Furness, John B.; Brock, James A.

doi:10.1152/ajpheart.00418.2012

Cited by 41 publications

(43 citation statements)

References 60 publications

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“…Moreover, macrophages and Th1 cells treated with cortistatin did not significantly change their capacity to bind to endothelial cells and to migrate to chemotactic stimuli, supporting that the effect of cortistatin is exerted at the endothelial level. Various studies indicate that endothelial cells express receptors for cortistatin and that they are able to respond to this neuropeptide4243.…”

Section: Discussionmentioning

confidence: 99%

Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells

Delgado-Maroto

Benítez

Forte-Lago

et al. 2017

Sci Rep

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Atherosclerosis is a chronic inflammatory cardiovascular disease that is responsible of high mortality worldwide. Evidence indicates that maladaptive autoimmune responses in the arterial wall play critical roles in the process of atherosclerosis. Cortistatin is a neuropeptide expressed in the vascular system and atherosclerotic plaques that regulates vascular calcification and neointimal formation, and inhibits inflammation in different experimental models of autoimmune diseases. Its role in inflammatory cardiovascular disorders is largely unexplored. The aim of this study is to investigate the potential therapeutic effects of cortistatin in two well-established preclinical models of atherosclerosis, and the molecular and cellular mechanisms involved. Systemic treatment with cortistatin reduced the number and size of atherosclerotic plaques in carotid artery, heart, aortic arch and aorta in acute and chronic atherosclerosis induced in apolipoprotein E-deficient mice fed a high-lipid diet. This effect was exerted at multiple levels. Cortistatin reduced Th1/Th17-driven inflammatory responses and increased regulatory T cells in atherosclerotic arteries and lymphoid organs. Moreover, cortistatin reduced the capacity of endothelial cells to bind and recruit immune cells to the plaque and impaired the formation of foam cells by enhancing cholesterol efflux from macrophages. Cortistatin emerges as a new candidate for the treatment of the clinical manifestations of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells

Delgado-Maroto

Benítez

Forte-Lago

et al. 2017

Sci Rep

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“…Data were recorded using SoftMax Pro ® 5.4. The mean of the peak fluorescence ratio after agonist injection minus the basal ratio was used for plotting concentration response curves as previously described [20]. …”

Section: Methodsmentioning

confidence: 99%

Effects of Food Components That Activate TRPA1 Receptors on Mucosal Ion Transport in the Mouse Intestine

et al. 2016

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TRPA1 is a ligand-activated cation channel found in the intestine and other tissues. Components of food that stimulate TRPA1 receptors (phytonutrients) include allyl isothiocyanate, cinnamaldehyde and linalool, but these may also act at other receptors. Cells lining the intestinal mucosa are immunoreactive for TRPA1 and Trpa1 mRNA occurs in mucosal extracts, suggesting that the TRPA1 receptor is the target for these agonists. However, in situ hybridisation reveals Trpa1 expression in 5-HT containing enteroendocrine cells, not enterocytes. TRPA1 agonists evoke mucosal secretion, which may be indirect (through release of 5-HT) or direct by activation of enterocytes. We investigated effects of the phytonutrients on transmucosal ion currents in mouse duodenum and colon, and the specificity of the phytonutrients in cells transfected with Trpa1, and in Trpa1-deficient mice. The phytonutrients increased currents in the duodenum with the relative potencies: allyl isothiocyanate (AITC) > cinnamaldehyde > linalool (0.1 to 300 μM). The rank order was similar in the colon, but linalool was ineffective. Responses to AITC were reduced by the TRPA1 antagonist HC-030031 (100 μM), and were greatly diminished in Trpa1−/− duodenum and colon. Responses were not reduced by tetrodotoxin, 5-HT receptor antagonists, or atropine, but inhibition of prostaglandin synthesis reduced responses. Thus, functional TRPA1 channels are expressed by enterocytes of the duodenum and colon. Activation of enterocyte TRPA1 by food components has the potential to facilitate nutrient absorption.

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“…BP-lowering effect of i.v. ghrelin administration in rats occurred together with a decrease in SNA and was not caused by the direct ghrelin action on blood vessels (Callaghan et al 2012). Moreover, a novel vascular receptor different from ghrelin receptor GHS-R1a was proposed to be involved in lowering of BP after the activation with growth hormone secretagogue analogs or ghrelin agonists in rats (Callaghan et al 2014).…”

Section: Peptides In Cardiovascular Regulationmentioning

confidence: 98%

Obesity-related hypertension: possible pathophysiological mechanisms

Vaněčková¹,

Maletı́nská²,

Behuliak³

et al. 2014

Journal of Endocrinology

129

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Hypertension is one of the major risk factors of cardiovascular diseases, but despite a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. The same is true for obesity, which is recognized as a major global epidemic health problem nowadays. Obesity is associated with an increasing prevalence of the metabolic syndrome, a cluster of risk factors including hypertension, abdominal obesity, dyslipidemia, and hyperglycemia. Epidemiological studies have shown that excess weight gain predicts future development of hypertension, and the relationship between BMI and blood pressure (BP) appears to be almost linear in different populations. There is no doubt that obesity-related hypertension is a multifactorial and polygenic trait, and multiple potential pathogenetic mechanisms probably contribute to the development of higher BP in obese humans. These include hyperinsulinemia, activation of the renin-angiotensin-aldosterone system, sympathetic nervous system stimulation, abnormal levels of certain adipokines such as leptin, or cytokines acting at the vascular endothelial level. Moreover, some genetic and epigenetic mechanisms are also in play. Although the full manifestation of both hypertension and obesity occurs predominantly in adulthood, their roots can be traced back to early ontogeny. The detailed knowledge of alterations occurring in the organism of experimental animals during particular critical periods (developmental windows) could help to solve this phenomenon in humans and might facilitate the age-specific prevention of human obesity-related hypertension. In addition, better understanding of particular pathophysiological mechanisms might be useful in so-called personalized medicine. Key Words" obesity " hypertension " sympathetic nervous system " renin-angiotensin system " critical developmental periods " epigenetics " rat

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Sites of action of ghrelin receptor ligands in cardiovascular control

Cited by 41 publications

References 60 publications

Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells

Cortistatin reduces atherosclerosis in hyperlipidemic ApoE-deficient mice and the formation of foam cells

Effects of Food Components That Activate TRPA1 Receptors on Mucosal Ion Transport in the Mouse Intestine

Obesity-related hypertension: possible pathophysiological mechanisms

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