Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Tsuda, Toshihide; Takefuji, Mikito; Wettschureck, Nina; Kotani, Kazuhiko; Morimoto, Ryo; Okumura, Takahiro; Kaur, Harmandeep; Eguchi, Shunsuke; Sakaguchi, Teruhiro; Ishihama, Sohta; Kikuchi, Ryosuke; Unno, Kazumasa; Matsushita, Kunihiro; Ishikawa, Shizukiyo; Offermanns, Stefan; Murohara, Toyoaki

doi:10.1084/jem.20161924

Cited by 31 publications

(37 citation statements)

References 69 publications

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“…Despite the gender differences observed in other peptides from the Ucn family and CRHR2, [39][40][41] there were no gender-related differences in plasma Ucn-2 levels in patients with heart disease, 19,21 nor in the role of CRHR2 in HF. 20 This was also true in our small cohort of patients.…”

Section: Discussionsupporting

confidence: 66%

“…Only three studies have measured plasmatic Ucn-2 levels in human patients with cardiovascular disorders, reporting significantly different (up to 1000-fold) concentrations in their cohorts. [18][19][20] However, Ucn-2 seems to be activated on circulating and inflammatory cells (buffy coat), which mediate vascular and myocardial remodelling mechanisms. 38 Also, we did not find any differences in the lung expression of Ucn-2 and CRHR2 in experimental PAH, suggesting a more profound dysregulation of Ucn-2/CRHR2 signalling in the RV as compared with the lung.…”

Section: Discussionmentioning

confidence: 99%

“…15 In patients with stable congestive 16 and acute decompensated HF, 17 intravenous Ucn-2 produces an increase in cardiac output (CO) and left ventricular (LV) ejection fraction (EF) in association with a reduction in systemic vascular resistance, blood pressure and cardiac work. Plasma levels of Ucn-2 are elevated in patients with abdominal aortic aneurysm, 18 LV systolic dysfunction with coronary artery disease 19 and nonischaemic dilated cardiomyopathy, 20 suggesting a potential role of Ucn-2 as a biomarker in heart disease. Additionally, plasma concentrations of N-terminal-proUcn-2 are independently and inversely related to 2-year survival in HF.…”

Section: Introductionmentioning

confidence: 99%

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Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Adão

Mendes-Ferreira

Santos‐Ribeiro

et al. 2018

Cardiovascular Research

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Section: Discussionsupporting

confidence: 66%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Adão

Mendes-Ferreira

Santos‐Ribeiro

et al. 2018

Cardiovascular Research

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“…33 A non-biased quantitative RT-PCR (qRT-PCR) analysis, which determined the gene copy numbers of 475 GPCRs in adult murine cardiomyocytes, revealed that CRHR2 was the 4th most abundantly expressed GPCR in cardiomyocytes. 34 In vitro, UCN2 and UCN3 significantly increase myocyte contractility in a dose-dependent manner, as characterized by increased fractional shortening and peak systolic Ca 2+ transients. 35 In rabbit and mouse ventricular myocytes, UCN2 mediates inotropic and lusitropic effects via the cAMP-and Ca 2+ /calmodulin-CaMKII signaling pathways, and also induces arrhythmogenic effects.…”

Section: Cardiac Effects Of Crhrsmentioning

confidence: 95%

“…39 Experiments involving administration of UCNs have revealed the inotropic effects of CRHR2 in the heart, but in conventional CRHR2 −/− mice and in cardiomyocyte-specific CRHR2 deficiency, basal cardiac function remains unaffected. 31,34 Thus, the physiological role of CRHR2 in basal cardiac function is still unclear.…”

Section: Crhrsmentioning

confidence: 99%

Corticotropin-Releasing Hormone Family and Their Receptors in the Cardiovascular System

Takefuji

Murohara

2019

Circ J

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acid precursor. 6 CRH plays a key role in regulating the basal and stress-induced pituitary-adrenal axis that increases glucocorticoid and androgen secretion. 7 CRH release in response to acute stress is essential for the survival of the organism, but CRH released as a result of exposure to chronic stress may influence emotions and exert negative effects on the homeostasis of the organism's physiological functions. 8 Urocortin 1 (UCN1),-2, and-3 were identified as a 2nd mammalian CRH family of peptides. Vaughan et al identified UCN1 in the Edinger-Westphal nucleus and lateral superior olive regions of the rat brain as a mammalian member of the mammalian CRH family of peptides. 9 The peptide was named UCN1 because of its homology with fish urotensin and CRH. UCN2 (38 amino acids) and UCN3 (38 amino acids) were identified as members of CRH-like peptides by searching human genome databases and cloning from human and mouse cDNA libraries. 10,11 Simultaneously, human stresscopin (N-terminally 2-amino acid extended UCN3) and stresscopin-related peptide (N-terminally 5-amino acid extended UCN2) were identified as members of the CRH family of peptides by Hsu et al. 12 Although CRH mRNA is expressed widely throughout the brain, UCN mRNA expression has restricted expression levels in the mammalian brain. 13 In peripheral tissue, UCN1 mRNA is broadly expressed in multiple organs, including the pituitary, gastrointestinal tract, testis, heart, G-protein coupled receptors (GPCRs) belong to the largest and most diverse superfamily of cell surface receptors. They react to extracellular stimuli and regulate cardiovascular (CV) function through cellular G-protein-mediated signaling. 1 GPCRs are a conserved family of 7 transmembrane receptors that have been targeted for drug therapy. 2 GPCRs are involved in cardiac dysfunction and hypertension, 3 and inhibitors of GPCRs are widely used to treat patients with CV diseases such as heart failure and hypertension. 4 Several studies have investigated various aspects of 2 GPCR families, β-adrenergic receptors and angiotensin II receptors, in CV diseases. There are approximately 800 GPCRs in humans, but the role of most of the GPCRs in CV diseases remains unclear, suggesting that uncharacterized GPCRs have considerable potential in the development of novel therapeutics for CV diseases. This review focuses on corticotropin-releasing hormone receptors (CRHRs) as potential therapeutic GPCRs in CV diseases, as well as their agonists and antagonists. Corticotropin-Releasing Hormone Family CRH, also named corticotropin-releasing factor, is a peptide that was first characterized from the ovine hypothalamus. 5 CRH is a 41-amino acid polypeptide (Figure) generated by the cleavage of the C-terminus of pre-proCRH, a 196-amino

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Circulating levels of urocortin neuropeptides are impaired in children with overweight

Kavalakatt

Khadir

Madhu

et al. 2022

Obesity

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The rise in the prevalence of childhood obesity is an increasing public health problem worldwide, particularly in societies that have witnessed a profound change in lifestyle associated with higher food intake and decreased physical activity during the past few decades (1). The number of children aged 5 to 19 years old living with obesity in 2019 is estimated to be 158 million worldwide and is expected to reach approximately 254 million by 2030 (2). These changes are accompanied by a rise in obesity-related metabolic disorders, including insulin resistance, dyslipidemia, and hormonal dysregulation (3). More alarmingly, nearly 80% of children and

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Corticotropin releasing hormone receptor 2 exacerbates chronic cardiac dysfunction

Cited by 31 publications

References 69 publications

Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Urocortin-2 improves right ventricular function and attenuates pulmonary arterial hypertension

Corticotropin-Releasing Hormone Family and Their Receptors in the Cardiovascular System

Circulating levels of urocortin neuropeptides are impaired in children with overweight

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