Cortistatin, a novel cardiovascular protective peptide

Liang, Juan Boo; Bai, Ying; Chen, Wen-Jia; Fu, Yu; Liu, Yue; Yin, Xinhua

doi:10.21037/cdt.2018.12.08

Cited by 14 publications

(9 citation statements)

References 43 publications

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“…Cortistatin is a neuropeptide that was originally found in the cerebral cortex and hypothalamus [ 35 ]. Recent studies have revealed that cortistatin is widely expressed in multiple systems and organs, such as the CNS and immune and endocrine systems [ 35 ]. Initially, cortistatin was found to be capable of depressing neuronal electricity [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy

Wen

Ding

Wang

et al. 2022

Journal of Immunology Research

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Sepsis-associated encephalopathy (SAE) is a life-threatening deterioration of mental status in relation to long-term and disabling cognitive dysfunction that is common in intensive care units worldwide. Cortistatin-14 is a neuropeptide structurally resembling somastostatin, which has been proven to play a crucial role in sepsis. The present study aimed to explore the neuroprotective role of cortistatin-14 in sepsis-associated encephalopathy and its underlying mechanisms in a mouse model. A septic mice model was established using the cecal ligation and puncture (CLP) method. The novel object recognition test (NORT), open field test (OFT), elevated plus maze test (EPMT), and tail suspension test (TST) were used to explore the behavioral performance of the mice. Transmission electron microscopy was used to observe the microstructure of the blood-brain barrier (BBB). Evans Blue staining was used to examine the integrity of the BBB. Immunofluorescence was used to examine the morphology and infiltration of microglia. A multiplex cytokine bead array assay was used to determine cytokine and chemokine levels in mouse serum and brain tissues. NORT revealed that cortistatin treatment improved cognitive impairment in septic mice. OFT, EPMT, and TST indicated that cortistatin-14 relieved the anxiety-related behaviors of CLP mice. In addition, cortistatin-14 treatment decreased the levels of various inflammatory cytokines, including interleukin-1β, interleukin-6, interferon-γ, and tumor necrosis factor-α in both the serum and brain of septic mice. Cortistatin reduced sepsis-induced blood-brain barrier disruption and inhibited microglial activation after the onset of sepsis. Cortistatin exerts neuroprotective effects against SAE and cognitive dysfunction in a CLP-induced mouse model of sepsis.

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Section: Discussionmentioning

confidence: 99%

Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy

Wen

Ding

Wang

et al. 2022

Journal of Immunology Research

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“…An increasing number of studies have indicated endogenous bioactive peptides play an important role in reducing myocardial injury and exerting cardioprotective effect (2). Cortistatin (CORT) is a new endogenous bioactive peptide originally found in the cerebral cortex and hypothalamus (3). Further studies indicated that CORT was widely expressed in the nervous, endocrine, and immune systems, and in areas such as the brain cortex, stomach, pancreas, monocytes, macrophages, and dendritic cells (3).…”

Section: Introductionmentioning

confidence: 99%

“…Cortistatin (CORT) is a new endogenous bioactive peptide originally found in the cerebral cortex and hypothalamus (3). Further studies indicated that CORT was widely expressed in the nervous, endocrine, and immune systems, and in areas such as the brain cortex, stomach, pancreas, monocytes, macrophages, and dendritic cells (3). CORT has been shown to exert multiple biological effects, including increased sleep, anti-nociception, antiinflammation, induction of immune tolerance, and regulation of endocrine and metabolism, through activating somatostatin receptors (SSTRs) and/or growth hormone secretagogue receptor 1a (GHSR1a) (3,4).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats

Chen¹,

Liang²,

Fu³

et al. 2020

Ann Transl Med

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Background: The present study was designed to examine whether cortistatin (CORT) could protect rats from myocardial injury induced by subcutaneously injecting isoproterenol (ISO) and to clarify the possible mechanisms. Methods: Male Sprague-Dawley (SD) rats were placed at random into four groups: the control group, the ISO group, the ISO + CORT 25 μg/(kg•d) group, and the ISO + CORT 50 μg/(kg•d) group. Rat models of myocardial injury were established with the subcutaneous (s.c.) injections of 85 mg/kg ISO for 2 days. In the ISO+ CORT 25 μg/(kg•d) group and ISO+ CORT 50 μg/(kg•d) group, rats were given s.c. injections of CORT 25 μg/(kg•d) and CORT 50 μg/(kg•d) on the day before ISO, 3 days, respectively. Serum malondialdehyde (MDA) content, lactate dehydrogenase (LDH) activity, and creatine kinase isoenzyme (CK-MB) activity were measured by corresponding test kits. Western blot was applied to evaluate the expression of endoplasmic reticulum stress-related protein glucose regulatory protein 78 (GRP78), enhancer-binding protein homologous protein (CHOP), cysteinyl aspartate specific proteinase-12 (caspase-12), LC3-II, Beclin-1, and p62 in the rat myocardium.Results: CORT alleviated the increased enzyme activities of serum LDH and CK-MB, and content of MDA (a typical marker of lipid peroxidation) in rats induced by ISO. CORT also prevented pathological myocardial injury in rats induced by ISO. Moreover, CORT attenuated the increased protein levels of GRP78, CHOP, and caspase-12, and reduced the increase of LC3-II, LC3-II/I, Beclin-1, and p62 in rats induced by ISO.Conclusions: These data demonstrate that CORT can attenuate ISO-induced acute myocardial injury in rats likely by reducing lipid peroxidation, and inhibiting endoplasmic reticulum stress and autophagy. This supports CORT as a potentially being a new target for preventing and treating myocardial injury and its related disease.

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“…Impaired angiogenesis is a main reason for insu ciency of nutrients and oxygen, which would cause loss of viability for resident cells of the femoral head 32 . CST is expressed in blood vessels and plays a critical role in the homeostasis of blood vessel function 33 . In this study, the ability of HUVECs to migrate and form tubes was retained by CST treatment in the stimulation of high-dose GCs.…”

Section: Discussionmentioning

confidence: 99%

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

Yuan

You

et al. 2022

Preprint

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Long-term use of glucocorticoids (GCs) is known to be a predominant cause of osteonecrosis of the femoral head (ONFH). Moreover, GCs can mediate apoptosis of various cell types by exaggerating oxidative stress. Previous studies have reported that the AKT pathway might be closely associated with apoptosis and metabolism of osteoblasts in ONFH mediated by GCs. We have previously found that cortistatin (CST) antagonizes oxidative stress and improves cell metabolism as well as apoptosis in several conditions. In this study, we detected that local and systemic CST expression levels were diminished in patients with ONFH compared with femoral neck fracture (FNF). In addition, a GC-induced rat ONFH model was established, which impaired bone quality and angiogenesis and improved osteoblastogenesis in the femoral head. Then, administration of CST attenuated these ONFH phenotypes in this model. Furthermore, osteoblast and endothelial cell lines were cultured and stimulated with dexamethasone (Dex) in the presence or absence of recombinant CST. As a result, Dex induced apoptosis and impaired anabolic metabolism of osteoblasts and suppressed tube formation as well as migration in endothelial cells, while additional treatment with CST reversed this damage to the cells. Moreover, blocking GHSR1a, a well-accepted receptor of CST, or blocking the AKT signaling pathway largely abolished the protective function of CST in Dex-induced disorder of the cells. Taken together, our results indicate that CST has the capability to prevent GC-induced apoptosis and metabolic disorder of osteoblasts in the pathogenesis of ONFH via the GHSR1a/AKT signaling pathway.

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Cortistatin, a novel cardiovascular protective peptide

Cited by 14 publications

References 43 publications

Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy

Cortistatin-14 Exerts Neuroprotective Effect Against Microglial Activation, Blood-brain Barrier Disruption, and Cognitive Impairment in Sepsis-associated Encephalopathy

Cardioprotection of cortistatin against isoproterenol-induced myocardial injury in rats

Cortistatin prevents glucocorticoid-associated osteonecrosis of the femoral head via the GHSR1a/Akt pathway

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