Do urocortins have a role in treating cardiovascular disease?

Chatzaki, Εkaterini; Kefala, Nikoleta; Drosos, Ioannis; Lalidou, Fani; Baritaki, Stavroula

doi:10.1016/j.drudis.2018.09.004

Cited by 8 publications

(17 citation statements)

References 49 publications

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“…These neuroendocrine peptides are best known for their involvement in regulating the physiological and behavioural responses to stress, through the cognate G-protein-coupled receptors (GPCRs), CRH receptor 1 (CRHR1) and CRH receptor 2 (CRHR2) (Chen et al 1993, Lovenberg et al 1995, Weninger et al 1999, Bakshi et al 2002, as part of the hypothalamic-pituitary-adrenal (HPA) axis. More recent evidence suggests additional, diverse, extra-hypothalamic roles for these peptides in peripheral organs (Paschos et al 2013, Chatoo et al 2018, Chatzaki et al 2019. Thus, CRH expression has been reported in the adrenal gland and the gastrointestinal tract (Suda et al 1984); UCN1 is expressed in heart, skin and adipose tissue (Kimura et al 2002, Seres et al 2004, Wierzbicka et al 2017; and UCN2 and UCN3 have been detected in peripheral blood cells, skeletal muscle, pancreas and gestational tissues such as foetal membranes and placental villi (Petraglia et al 2010).…”

Section: Introductionmentioning

confidence: 99%

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

Simpson

Smith

Jones

et al. 2020

Journal of Endocrinology

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The corticotropin-releasing hormone (CRH) family of peptides, including urocortin (UCN) 1, 2 and 3, are established hypothalamic neuroendocrine peptides, regulating the physiological and behaviour responses to stress indirectly, via the hypothalamic-pituitary-adrenal (HPA) axis. More recently, these peptides have been implicated in diverse roles in peripheral organs through direct signalling, including in placental and pancreatic islet physiology. CRH has been shown to stimulate insulin release through activation of its cognate receptors, CRH receptor 1 (CRHR1) and 2. However, the physiological significance of this is unknown. We have previously reported that during mouse pregnancy, expression of CRH peptides increase in mouse placenta suggesting that these peptides may play a role in various biological functions associated with pregnancy, particularly the pancreatic islet adaptations that occur in the pregnant state to compensate for the physiological increase in maternal insulin resistance. In the current study, we show that mouse pregnancy is associated with increased circulating levels of UCN2 and that when we pharmacologically block endogenous CRHR signalling in pregnant mice, impairment of glucose tolerance is observed. This effect on glucose tolerance was comparable to that displayed with specific CRHR2 blockade and not with specific CRHR1 blockade. No effects on insulin sensitivity or the proliferative capacity of β-cells were detected. Thus, CRHR2 signalling appears to be involved in β-cell adaptive responses to pregnancy in the mouse, with endogenous placental UCN2 being the likely signal mediating this.

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Section: Introductionmentioning

confidence: 99%

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

Simpson

Smith

Jones

et al. 2020

Journal of Endocrinology

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“… 75 , 76 The urocortin system, which is extensively expressed in the CNS and plays a role in HPA axis as well as counter-regulation response to hypoglycemia, 77 and energy homeostasis, 78 was recently reported to have potential in regulating cardiovascular activity. 79 Previous studies have also shown that estrogens, which centrally affect glucose homeostasis, could activate estrogen receptor α (Erα) thereby contributing to cardiometabolic protection. 80–82 These data affirm that neuropeptides or hormones that influence energy and metabolism could be playing critical roles in ANS, and have functional convergences in cardiovascular control.…”

Section: The Relationship Between Central Energy Mechanism and Cardiovascular Regulationmentioning

confidence: 99%

An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is)

Nguyen

Gong

et al. 2021

DMSO

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GLP-1 receptor agonists (GLP-1RAs) and SGLT-2 inhibitors (SGLT-2is) are novel antidiabetic medications associated with considerable cardiovascular benefits therapying treatment of diabetic patients. GLP-1 exhibits atherosclerosis resistance, whereas SGLT-2i acts to ameliorate the neuroendocrine state in the patients with chronic heart failure. Despite their distinct modes of action, both factors share pathways by regulating the central nervous system (CNS). While numerous preclinical and clinical studies have demonstrated that GLP-1 can access various nuclei associated with energy homeostasis and hedonic eating in the CNS via blood–brain barrier (BBB), research on the activity of SGLT-2is remains limited. In our previous studies, we demonstrated that both GLP-1 receptor agonists (GLP-1RAs) liraglutide and exenatide, as well as an SGLT-2i, dapagliflozin, could activate various nuclei and pathways in the CNS of Sprague Dawley (SD) rats and C57BL/6 mice, respectively. Moreover, our results revealed similarities and differences in neural pathways, which possibly regulated different metabolic effects of GLP-1RA and SGLT-2i via sympathetic and parasympathetic systems in the CNS, such as feeding, blood glucose regulation and cardiovascular activities (arterial blood pressure and heart rate control). In the present article, we extensively discuss recent preclinical studies on the effects of GLP-1RAs and SGLT-2is on the CNS actions, with the aim of providing a theoretical explanation on their mechanism of action in improvement of the macro-cardiovascular risk and reducing incidence of diabetic complications. Overall, these findings are expected to guide future drug design approaches.

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“…8 Urocortin-1 is predominantly expressed in the Edinger Westphal nucleus, the hypothalamus and in the supraoptic nuclei of the brain. 8,9 At the periphery, urocortin-1 is found in the intestine, liver, cardiomyocytes, thymus, skin, spleen and immune cells. 8,9 Urocortin-2 is expressed in the hypothalamus, brainstem and spinal cord 8 and at the periphery, it is found in the gastrointestinal tract, the heart, coronary arteries, thymus, blood cells and adrenal glands.…”

Section: Localization Of Crh and Urocortins In Organs And Tissuesmentioning

confidence: 99%

“…8,9 At the periphery, urocortin-1 is found in the intestine, liver, cardiomyocytes, thymus, skin, spleen and immune cells. 8,9 Urocortin-2 is expressed in the hypothalamus, brainstem and spinal cord 8 and at the periphery, it is found in the gastrointestinal tract, the heart, coronary arteries, thymus, blood cells and adrenal glands. 8,9 Urocortin-3 is found in the hypothalamus and amygdala, the intestine and pancreas.…”

Section: Localization Of Crh and Urocortins In Organs And Tissuesmentioning

confidence: 99%

“…8,9 Urocortin-2 is expressed in the hypothalamus, brainstem and spinal cord 8 and at the periphery, it is found in the gastrointestinal tract, the heart, coronary arteries, thymus, blood cells and adrenal glands. 8,9 Urocortin-3 is found in the hypothalamus and amygdala, the intestine and pancreas. 8 All 3 urocortins have been detected in the heart.…”

Section: Localization Of Crh and Urocortins In Organs And Tissuesmentioning

confidence: 99%

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Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling

Popov

Прокудина

Mukhomedzyanov

et al. 2021

J Cardiovasc Pharmacol Ther

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Despite the recent progress in research and therapy, cardiovascular diseases are still the most common cause of death worldwide, thus new approaches are still needed. The aim of this review is to highlight the cardioprotective potential of urocortins and corticotropin-releasing hormone (CRH) and their signaling. It has been documented that urocortins and CRH reduce ischemic and reperfusion (I/R) injury, prevent reperfusion ventricular tachycardia and fibrillation, and improve cardiac contractility during reperfusion. Urocortin-induced increase in cardiac tolerance to I/R depends mainly on the activation of corticotropin-releasing hormone receptor-2 (CRHR2) and its downstream pathways including tyrosine kinase Src, protein kinase A and C (PKA, PKCε) and extracellular signal-regulated kinase (ERK1/2). It was discussed the possibility of the involvement of interleukin-6, Janus kinase-2 and signal transducer and activator of transcription 3 (STAT3) and microRNAs in the cardioprotective effect of urocortins. Additionally, phospholipase-A2 inhibition, mitochondrial permeability transition pore (MPT-pore) blockade and suppression of apoptosis are involved in urocortin-elicited cardioprotection. Chronic administration of urocortin-2 prevents the development of postinfarction cardiac remodeling. Urocortin possesses vasoprotective and vasodilator effect; the former is mediated by PKC activation and prevents an impairment of endothelium-dependent coronary vasodilation after I/R in the isolated heart, while the latter includes both cAMP and cGMP signaling and its downstream targets. As CRHR2 is expressed by both cardiomyocytes and vascular endothelial cells. Urocortins mediate both endothelium-dependent and -independent relaxation of coronary arteries.

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Do urocortins have a role in treating cardiovascular disease?

Cited by 8 publications

References 49 publications

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

UCN2: a new candidate influencing pancreatic β-cell adaptations in pregnancy

An Overview of Similarities and Differences in Metabolic Actions and Effects of Central Nervous System Between Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RAs) and Sodium Glucose Co-Transporter-2 Inhibitors (SGLT-2is)

Cardioprotective and Vasoprotective Effects of Corticotropin-Releasing Hormone and Urocortins: Receptors and Signaling

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