Ghrelin and vascular protection

Pearson, James T.; Shirai, Masamitsu; Sukumaran, Vijayakumar; Du, Cheng-Kun; Tsuchimochi, Hirotsugu; Sonobe, Takashi; Waddingham, Mark T.; Katare, Rajesh; Schwenke, Daryl O.

doi:10.1530/vb-19-0024

Cited by 7 publications

(9 citation statements)

References 39 publications

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“…In this study, we provide direct evidence that hexarelin act as a vasodilator in the healthy rat coronary microcirculation, and that this involved activation of the GHS-R1a receptor pathway as reported for ghrelin (Pearson et al, 2019). Furthermore, for the first time in a PH model, we show that: (1) more myosin heads appeared to become super-relaxed, with displacement away from actin binding sites, while (2) myosin interfilament spacing at diastole was additively reduced by the combination of PH and chronic hexarelin treatment.…”

Section: Discussionsupporting

confidence: 70%

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models

et al. 2022

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The majority of the conventional techniques that are utilized for investigating the pathogenesis of cardiovascular disease in preclinical animal models do not permit microlevel assessment of in situ cardiomyocyte and microvascular functions. Therefore, it has been difficult to establish whether cardiac dysfunction in complex multiorgan disease states, such as heart failure with preserved ejection fraction and pulmonary hypertension, have their origins in microvascular dysfunction or rather in the cardiomyocyte. Herein, we describe our approach of utilizing synchrotron radiation microangiography to, first, ascertain whether the growth hormone secretagogue (GHS) hexarelin is a vasodilator in the coronary circulation of normal and anesthetized Sprague-Dawley rats, and next investigate if hexarelin is able to prevent the pathogenesis of right ventricle (RV) dysfunction in pulmonary hypertension in the sugen chronic hypoxia model rat. We show that acute hexarelin administration evokes coronary microvascular dilation through GHS-receptor 1a and nitric oxide, and through endothelium-derived hyperpolarization. Previous work indicated that chronic exogenous administration of ghrelin largely prevented the pathogenesis of pulmonary hypertension in chronic hypoxia and in monocrotaline models. Unexpectedly, chronic hexarelin administration prior to sugen chronic hypoxia did not prevent RV hypertrophy or RV cardiomyocyte relaxation impairment. Small-angle X-ray scattering revealed that super relaxed myosin filaments contributed to diastolic dysfunction, and that length-dependent activation might contribute to sustained contractility of the RV. Thus, synchrotron-based imaging approaches can reveal novel insights into cardiac and coronary functions in vivo.

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Section: Discussionsupporting

confidence: 70%

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models

et al. 2022

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“…Similar to our study, some studies have shown that ghrelin can inhibit vascular endothelial cell angiogenesis [ 30 , 31 ]; however, other studies have found opposite results suggesting that ghrelin can boost angiogenesis [ 32 , 33 ]. Taking these findings together, we hypothesized that ghrelin has a protective effect on vascular endothelial cells [ 34 ] and maintains cellular homeostasis under pathological conditions by regulating—either promoting or inhibiting—angiogenesis [ 15 ], for cells to better adapt to the environment.…”

Section: Discussionmentioning

confidence: 99%

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

Yao

Zhou

et al. 2022

Eye and Vis

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Background To investigate the effect of ghrelin, a brain-gut peptide hormone, on high glucose-induced retinal angiogenesis in vitro and explore its association with endoplasmic reticulum (ER) stress. Methods Human retinal microvascular endothelial cells (HRMECs) were first divided into control and high-glucose groups, and the mRNA and protein expression levels of the receptor for ghrelin [growth hormone secretin receptor 1a, (GHSR-1a)] in cells were determined. HRMECs were then treated with high glucose alone or in combination with ghrelin or siGHSR-1a, and cell viability, migration, tube formation and the expression of the ER stress-related proteins PERK, ATF4 and CHOP were detected. Finally, to clarify whether the effects of ghrelin are related to ER stress, tunicamycin, an inducer of ER stress, was used to treat HRMECs, and cell viability, cell migration, and tube formation were evaluated. Results GHSR-1a expression in HRMECs at both the mRNA and protein levels was inhibited by high-glucose treatment. Under high-glucose conditions, ghrelin promoted cell viability and inhibited migration and tube formation, which were blocked by siGHSR-1a treatment. Ghrelin inhibited the increases in the protein levels of p-PERK, ATF4 and CHOP induced by high-glucose treatment, and combination treatment with siGHSR-1a reversed this effect of ghrelin. When tunicamycin was added, the effects of ghrelin on cell viability, migration and tube formation were all weakened. Conclusions This study experimentally revealed that ghrelin can inhibit high glucose-induced retinal angiogenesis in vitro through GHSR-1a, and alleviation of ER stress may be one of the mechanisms underlying this effect.

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“…Ghrelin is produced by the stomach, heart, lung, and kidney and has extensive physiological effects, such as stimulating growth hormone secretion, promoting food intake, and maintaining energy homeostasis. Emerging evidence has shown favorable effects of ghrelin on cardiovascular function via either growth hormone-dependent or -independent mechanisms [ 116 , 117 ].…”

Section: Vasoactive Peptides and Vascular Aging-related Diseasesmentioning

confidence: 99%

“…Emerging evidence has shown favorable effects of ghrelin on cardiovascular function [ 116 , 117 ]. Ghrelin rescued the activity of SIRT1 and the expression of superoxide dismutase-2 (SOD-2), a primary enzymatic antioxidant defense against ROS production, and resulted in great attenuation of EC senescence in mice [ 119 ].…”

Section: Vasoactive Peptides and Vascular Aging-related Diseasesmentioning

confidence: 99%

Endogenous Vasoactive Peptides and Vascular Aging-Related Diseases

Chen

2022

Oxidative Medicine and Cellular Longevity

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Vascular aging is a specific type of organic aging that plays a central role in the morbidity and mortality of cardiovascular and cerebrovascular diseases among the elderly. It is essential to develop novel interventions to prevent/delay age-related vascular pathologies by targeting fundamental cellular and molecular aging processes. Endogenous vasoactive peptides are compounds formed by a group of amino acids connected by peptide chains that exert regulatory roles in intercellular interactions involved in a variety of biological and pathological processes. Emerging evidence suggests that a variety of vasoactive peptides play important roles in the occurrence and development of vascular aging and related diseases such as atherosclerosis, hypertension, vascular calcification, abdominal aortic aneurysms, and stroke. This review will summarize the cumulative roles and mechanisms of several important endogenous vasoactive peptides in vascular aging and vascular aging-related diseases. In addition, we also aim to explore the promising diagnostic function as biomarkers and the potential therapeutic application of endogenous vasoactive peptides in vascular aging-related diseases.

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Ghrelin and vascular protection

Cited by 7 publications

References 39 publications

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models

Using Synchrotron Radiation Imaging Techniques to Elucidate the Actions of Hexarelin in the Heart of Small Animal Models

The ghrelin-GHSR-1a pathway inhibits high glucose-induced retinal angiogenesis in vitro by alleviating endoplasmic reticulum stress

Endogenous Vasoactive Peptides and Vascular Aging-Related Diseases

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