Search

Background/Objectives: Anthracyclines remain a pivotal element of numerous tumor management regimens; however, their utilization is associated with a range of adverse effects, the most significant of which is cardiotoxicity. Research is constantly being conducted to identify substances that could be incorporated into ongoing cancer chemotherapy to mitigate anthracycline-induced cardiotoxicity. Recently, the apelinergic system has received a lot of attention in this field due to its involvement in cardiovascular regulation. Therefore, the aim of our study was to investigate the ability of the apelinergic system to inhibit the cardiotoxic effects of anthracycline—doxorubicin (DOX). Methods: In this study, 54 Sprague–Dawley rats were divided into seven groups and received intraperitoneal injections with DOX once a week for 4 consecutive weeks. The osmotic pumps provided a continuous release of NaCl (control groups), apelin-13 and elabela at two different doses, and the apelin receptor (APJ) antagonist ML221. Electrocardiography (ECG) and transthoracic echocardiography (TTE) with assessment of left ventricular (LV) systolic parameters were conducted on the first and last days of the experiment. Results: Lower doses of APJ agonists prevented the prolongation of QT and QTc intervals induced by DOX, while higher doses of these drugs exerted no such effect. The TTE examination confirmed DOX-induced LV systolic dysfunction. Moreover, the TTE examination revealed an improvement in the LV systolic parameters in the DOX-treated groups that were simultaneously administered APJ agonists. Conclusions: Our findings support the use of apelin and elabela as potential cardioprotective agents against anthracycline-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Cancer is the leading cause of death worldwide, and the number of cancer-related deaths is expected to increase. Common types of cancer include skin, breast, lung, prostate, and colorectal cancers. While clinical research has improved cancer therapies, these treatments often come with significant side effects such as chronic fatigue, hair loss, and nausea. In addition, cancer treatments can cause long-term cardiovascular complications. Doxorubicin (DOX) therapy is one example, which can lead to decreased left ventricle (LV) echocardiography (ECHO) parameters, increased oxidative stress in cellular level, and even cardiac fibrosis. The apelinergic system, specifically apelin and its receptor, together, has shown properties that could potentially protect the heart and mitigate the damages caused by DOX anti-cancer treatment. Studies have suggested that stimulating the apelinergic system may have therapeutic benefits for heart damage induced by DOX. Further research in chronic preclinical models is needed to confirm this hypothesis and understand the mechanism of action for the apelinergic system. This review aims to collect and present data on the effects of the apelinergic system on doxorubicin-induced cardiotoxicity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Anthracyclines remain a pivotal element of numerous tumor management regimens; however, their utilization is associated with a range of adverse effects, the most significant of which is cardiotoxicity. Research is constantly being conducted to identify substances that could be incorporated into ongoing cancer chemotherapy to mitigate anthracycline-induced cardiotoxicity. Recently, the apelinergic system has received a lot of attention in this field due to its involvement in cardiovascular regulation. Therefore, the aim of our study was to investigate the ability of the apelinergic system to inhibit the cardiotoxic effects of anthracycline—doxorubicin (DOX). Methods: In this study, 54 Sprague–Dawley rats were divided into seven groups and received intraperitoneal injections with DOX once a week for 4 consecutive weeks. The osmotic pumps provided a continuous release of NaCl (control groups), apelin-13 and elabela at two different doses, and the apelin receptor (APJ) antagonist ML221. Electrocardiography (ECG) and transthoracic echocardiography (TTE) with assessment of left ventricular (LV) systolic parameters were conducted on the first and last days of the experiment. Results: Lower doses of APJ agonists prevented the prolongation of QT and QTc intervals induced by DOX, while higher doses of these drugs exerted no such effect. The TTE examination confirmed DOX-induced LV systolic dysfunction. Moreover, the TTE examination revealed an improvement in the LV systolic parameters in the DOX-treated groups that were simultaneously administered APJ agonists. Conclusions: Our findings support the use of apelin and elabela as potential cardioprotective agents against anthracycline-induced cardiotoxicity.

Background: There is a growing body of evidence for an important role of the apelinergic system in the modulation of cardiovascular homeostasis. The aim of our study was to (1) examine the relationship between apelin serum concentration at index myocardial infarction (MI) and atrioventricular conduction disorders (AVCDs) at 12-month follow-up, and (2) investigate the association between initial apelin concentration and the novel marker of post-MI scar (Q/QRS ratio) at follow-up. Methods: In 84 patients with MI with complete revascularization, apelin peptide serum concentrations for apelin-13, apelin-17, elabela (ELA) and apelin receptor (APJ) were measured on day one of hospitalization; at 12-month follow-up, 54 of them underwent thorough examination that included 12-lead electrocardiography (ECG), Holter ECG monitoring and echocardiography. Results: The mean age was 58.9 years. At 12-month follow-up, AVCDs were diagnosed in 21.4% of subjects, with AV first-degree block in 16.7% and sinoatrial arrest in 3.7%. ELA serum concentration at index MI correlated positively with the occurrence of AVCD (p = 0.003) and heart rate (p = 0.005) at 12-month follow-up. The apelin-13 serum concentration at index MI correlated negatively with the Q/QRS ratio. Conclusions: The apelin peptide concentration during an acute phase of MI impacts the development of AVCD and the value of Q/QRS ratio in MI survivors. [ABSTRACT FROM AUTHOR]

Aim: Pulpal pain is a common orofacial health issue that has been linked to cognitive impairment. Because of its prominent role in pain modulation and cognitive impairment, apelin (Apl) is regarded as a promising target for clinical pain management. The role of Apl in orofacial pain, however, is unknown. The purpose of this study was to determine the effects of intra‐periaqueductal grey matter (PAG) administrations of Apl‐13 on capsaicin‐evoked pulpal nocifensive behaviour and capsaicin‐induced spatial learning and memory impairments in rats. Methodology: Forty‐nine male Wistar rats (200–250 g) were randomly divided into seven groups (n = 7 per group). The groups included: untreated intact, capsaicin (Caps) only, three Caps+Apl groups that received different dosages of intra‐PAG injection of Apl‐13 (1, 2 and 3 μg/rat) 20 min prior to capsaicin application, and two Apl+antagonist groups that received Apl receptor antagonist or naloxone (a μ opioid receptor) 20 min before Apl injection. Learning and memory were assessed using the Morris water maze test. One‐way analysis of variance followed by Tukey post hoc tests was used for statistical analysis. Results: Intra‐PAG administration of Apl‐13 significantly reduced the capsaicin‐induced nocifensive behaviour (p <.01). This antinociception effect was inhibited by F13A and naloxone. Apl‐13 inhibited nociception‐induced learning and memory deficits (p <.01). The cognitive effects were also blocked by pre‐treatment administration of F13A (3 μg/rat). Conclusions: These findings indicated that Apl‐13, via Apl receptors (AR or APJ) and μ opioid receptors, alleviated capsaicin‐induced dental nocifensive behaviour and protected against nociception‐induced learning and memory impairments. As a result of our findings, Apl appears to be a promising analgesic option for further research in orofacial pain models and clinical trials. [ABSTRACT FROM AUTHOR]

Water balance in the body is achieved by balancing renal and non-renal water losses with corresponding water intake. It is under the control of both the central nervous system, which integrates many parameters of water and electrolyte balance in the body, including inducing important adaptive behavioral responses, and three hormonal systems: vasopressinergic, renin-angiotensin-aldosterone and apelinergic. A lot of research is devoted to the regulation of water-electrolyte metabolism. However, this process is still quite difficult to understand, especially since more and more of its regulators are being discovered over time. One of them is the hormone apelin, an endogenous ligand for the APJ receptor. As is known, the receptor is highly expressed in many organs, such as the brain, heart, liver and kidneys, lungs, and has multidirectional effects.This literature review discusses the main characteristics and features of the regulation of these systems in relation to water-electrolyte metabolism, as well as issues of intersystem interaction and modulation of the effects of apelin.

IntroductionPeripheral arterial disease (PAD) is a major risk factor for lower-extremity amputation in diabetic patients. Unfortunately, previous clinical studies investigating therapeutic angiogenesis using the vascular endothelial growth factor (VEGF) have shown disappointing results in diabetic patients, which evokes the necessity for novel therapeutic agents. The apelinergic system (APJ receptor/apelin) is highly upregulated under hypoxic condition and acts as an activator of angiogenesis. Apelin treatment improves revascularization in nondiabetic models of ischemia, however, its role on angiogenesis in diabetic conditions remains poorly investigated. This study explored the impact of Pyr-apelin-13 in endothelial cell function and diabetic mouse model of hindlimb ischemia.MethodsNondiabetic and diabetic mice underwent femoral artery ligation to induce limb ischemia. Diabetic mice were implanted subcutaneously with osmotic pumps delivering Pyr-apelin-13 for 28 days. Blood flow reperfusion was measured for 4 weeks post-surgery and exercise willingness was assessed with voluntary wheels. In vitro, bovine aortic endothelial cells (BAECs) were exposed to normal (NG) or high glucose (HG) levels and hypoxia. Cell migration, proliferation and tube formation assays were performed following either VEGF or Pyr-apelin-13 stimulation.Results and DiscussionFollowing limb ischemia, blood flow reperfusion, functional recovery of the limb and vascular density were improved in diabetic mice receiving Pyr-apelin-13 compared to untreated diabetic mice. In cultured BAECs, exposure to HG concentrations and hypoxia reduced VEGF proangiogenic actions, whereas apelin proangiogenic effects remained unaltered. Pyr-apelin-13 induced its proangiogenic actions through Akt/AMPK/eNOS and RhoA/ROCK signaling pathways under both NG or HG concentrations and hypoxia exposure. Our results identified the apelinergic system as a potential therapeutic target for angiogenic therapy in diabetic patients with PAD.

Background: Although the bioactive peptides associated with the apelinergic system are known to be associated with heart failure and ischemic heart disease, there are no data on their association with acromegaly. Aim: We aimed to investigate the change in serum Elabela levels, a novel peptide of the apelinergic system, in patients with acromegaly. Methods: Our study included 30 treatment naive patients who were recently diagnosed with acromegaly, and 50 age-and-sex-matched healthy controls. In addition to routine history, physical examination and laboratory examinations, serum Elabela level was measured. Participants were divided into two groups as individuals with and without acromegaly and compared to each other. Results: Diastolic blood pressure (DBP) and systolic blood pressure (SBP) were found to be higher in patients with acromegaly. Serum glucose, Hs-CRP, NT-proBNP, insulin-like growth factor-1, growth hormone and serum Elabela levels were higher in patients with acromegaly (p < 0.05 for each). Left ventricular ejection fraction (LV-EF) was found to be lower in patients with acromegaly than the patients in healthy control group (p < 0.05). In multivariate analysis; age, systolic blood pressure, NT-proBNP, Insulin-like growth factor 1 and growth hormone levels were found to be very closely and positively related to serum Elabela level (p < 0.05 for each). Conclusions: Serum Elabela level can be used as an early and objective indicator of early cardiovascular involvement in patients with acromegaly. Further research is needed to clarify the role of serum Elabela levels on cardiovascular system in acromegaly patients. [ABSTRACT FROM AUTHOR]

Apelin is an endogenous ligand for the G protein-coupled receptor APJ and has multiple biological activities in human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. This article reviews the crucial role of apelin in regulating oxidative stress-related processes by promoting prooxidant or antioxidant mechanisms. Following the binding of APJ to different active apelin isoforms and the interaction with several G proteins according to cell types, the apelin/APJ system is able to modulate different intracellular signaling pathways and biological functions, such as vascular tone, platelet aggregation and leukocytes adhesion, myocardial activity, ischemia/reperfusion injury, insulin resistance, inflammation, and cell proliferation and invasion. As a consequence of these multifaceted properties, the role of the apelinergic axis in the pathogenesis of degenerative and proliferative conditions (e.g., Alzheimer's and Parkinson's diseases, osteoporosis, and cancer) is currently investigated. In this view, the dual effect of the apelin/APJ system in the regulation of oxidative stress needs to be more extensively clarified, in order to identify new potential strategies and tools able to selectively modulate this axis according to the tissue-specific profile. [ABSTRACT FROM AUTHOR]

Apelin is an endogenous peptide ligand for G protein coupled apelin receptors (APJ orphan receptors) which are very similar to angiotensin II receptors. Apelin is expressed in most tissues of the body including hypothalamus that is responsible for regulating water and food intake, the gastrointestinal tract, the circulatory system, adipose and muscle tissues, and the immune system. The physiological actions of apelin, including food intake, has not yet been reported in birds. In this study, the effect of intracerebroventricular injection of different doses of apelin-13 was investigated on food intake in neonatal broilers at the age of five and seven days. The chicks had access to food immediately after injection and cumulative food intake was measured at half, 1, 2, 3, 4, 8 and 21 hr after injection. The 2-way ANOVA analyzed data showed that apelin-13 at dose of 1.00 μg significantly reduced food intake at 21 hr after injection in five-day old chicks. In addition, in dose of 1.50 μg, it could significantly reduce food intake at 2, 3, 4, 8 and 21 hr after injection. In seven-day-old chicks, the doses of 1.00 and 4.00 μg of apelin-13 had no effect on food intake compared to the control group. Apelin-13 at dose of 2.00 μg significantly reduced food intake at 8 and 21 hr after injection. The results of this study showed that apelin-13 had a reducing effect on food consumption in neonatal broiler chicks. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) has emerged as a global health crisis, surpassing mortality rates associated with several cancers and heart failure. The lack of effective therapies, coupled with challenges in diagnosis and the high cost of kidney transplantation, underscores the urgent need to explore novel therapeutic targets and strategies for AKI. Understanding the intricate pathophysiology of AKI is paramount in this endeavor. The components of the apelinergic system—namely, apelin and elabela/toddler, along with their receptor—are prominently expressed in various kidney cells and have garnered significant attention in renal research. Recent studies have highlighted the renoprotective role of the apelinergic system in AKI. This system exerts its protective effects by modulating several pathophysiological processes, including reducing endoplasmic reticulum (ER) stress, improving mitochondrial dynamics, inhibiting inflammation and apoptosis, promoting diuresis through vasodilation of renal vasculature, and counteracting the effects of reactive oxygen species (ROS). Despite these advancements, the precise involvement of the apelinergic system in the progression of AKI remains unclear. Furthermore, the therapeutic potential of apelin-13 in AKI is not fully understood. This review aims to elucidate the role of the apelinergic system in AKI and its interactions with key pathomechanisms involved in the progression of AKI. Additionally, we discuss the current clinical status of exogenous apelin-13 therapy, providing insights that will guide future research on apelin against AKI. [Display omitted] [ABSTRACT FROM AUTHOR]

The apelinergic system comprises two peptide ligands, apelin and ELABELA, and their cognate G-protein-coupled receptor, the apelin receptor APJ. Apelin is a peptide that was isolated from bovine stomach extracts; the distribution of the four main active forms, apelin-36, -17, -13, and pyr-apelin-13 differs between tissues. The mature form of ELABELA-32 can be transformed into forms called ELABELA-11 or -21. The biological function of the apelinergic system is multifaceted, and includes the regulation of angiogenesis, body fluid homeostasis, energy metabolism, and functioning of the cardiovascular, nervous, respiratory, digestive, and reproductive systems. This review summarises the mechanism of the apelinergic system in cell apoptosis. Depending on the cell/tissue, the apelinergic system modulates cell apoptosis by activating various signalling pathways, including phosphoinositide 3-kinase (PI3K), extracellular signal-regulated protein kinase (ERK1/2), protein kinase B (AKT), 5'AMP-activated protein kinase(AMPK), and protein kinase A (PKA). Apoptosis is critically important during various developmental processes, and any dysfunction leads to pathological conditions such as cancer, autoimmune diseases, and developmental defects. The purpose of this review is to present data that suggest a significant role of the apelinergic system as a potential agent in various therapies. [ABSTRACT FROM AUTHOR]

Abstract Background It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum ELABELA levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment. Methods Forty two untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FİNLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer’s instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels. Results In our study, we found that serum ELA levels were significantly higher in patients with CLL. Conclusions This study highlights that ELA targeting may be a potential therapeutic option for treating CLL.

The apelinergic system plays an important role in the modulation of the cardiovascular system via the apelin peptide and the apelin receptor (APJ receptor). Apelin and elabela, also known toddler, are peptide ligands for the apelin receptor. These two peptides show similar biological actions, such as vasodilatation, increased myocardial contractility, angiogenesis, and energy metabolism. However, the serum levels of elabela in patients with hyperthyroidism are not well known. The aim of this study was to investigate the changes in serum elabela levels in patients with hyperthyroidism and its association with hypertension. This cross-sectional study included 74 patients with newly diagnosed hyperthyroidism due to Graves' disease and 20 healthy individuals. Serum elabela levels were measured by enzyme-linked immunosorbent assay. The patients were divided into two groups: hyperthyroid patients without hypertension (n = 51) and those with hypertension (n = 23). Basal heart rate, serum glucose and highsensitive C reactive protein were significantly higher in hyperthyroid patients with and those without hypertension than in healthy controls (p < 0.05 for each). Serum elabela levels were significantly elevated in hyperthyroid patients compared with healthy controls, with higher serum elabela levels found in hyperthyroid patients with hypertension than those without hypertension. Linear regression analysis showed that serum elabela levels were correlated with systolic blood pressure (p < 0.001). In conclusion, serum elabela levels were significantly increased in patients with hyperthyroidism, especially in hyperthyroid patients with hypertension. Elevation in serum elabela levels may contribute to alleviation of cardiovascular complications of hyperthyroidism and hypertension. [ABSTRACT FROM AUTHOR]

The apelinergic system, which includes the apelin receptor (APJ) as well as its two specific ligands, namely apelin and ELABELA (ELA/APELA/Toddler), have been the subject of many recent studies due to their pleiotropic effects in humans and other animals. Expression of these factors has been investigated in numerous tissues and organs—for example, the lungs, heart, uterus, and ovary. Moreover, a number of studies have been devoted to understanding the role of apelin and the entire apelinergic system in the most important processes in the body, starting from early stages of human life with regulation of placental function and the proper course of pregnancy. Disturbances in the balance of placental processes such as proliferation, apoptosis, angiogenesis, or hormone secretion may lead to specific pregnancy pathologies; therefore, there is a great need to search for substances that would help in their early diagnosis or treatment. A number of studies have indicated that compounds of the apelinergic system could serve this purpose. Hence, in this review, we summarized the most important reports about the role of apelin and the entire apelinergic system in the regulation of placental physiology and pregnancy.

Abstract Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the “maintaining blood pressure” paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock.

Background: It has been shown that bcl2, bcl-XL and mcl-1 protein levels are high in chronic lymphocytic leukemia cells, and resultantly, apoptosis does not occur chronic lymphocytic leukemia cells. Apelin and apela (ELABELA/ELA/Toddler) are two peptide ligands for a class A G-protein coupled receptor called apelin receptor. Studies have shown that ELA inhibits apoptosis by inhibiting apoptotic proteins and activating anti-apoptotic proteins. Proteins and genes involved in apoptosis are valuable for targeted cancer therapy. We hypothesized that serum levels may be increased in patients with chronic lymphocytic leukemia based on the antiapoptotic effect of ELA. We compared serum ELABELA levels of healthy volunteers and patients with chronic lymphocytic leukemia. We aimed to draw attention to a new molecule worthy of research in targeted cancer treatment.Methods: Forty two untreated CLL patients and 41 healthy volunteers were included in the study. Serum ELA levels were measured by using enzyme-linked immunosorbent assay kits (Dhanghai Sunred Biological Technology co. Ltd), automated ELISA reader (Thermo Scientific, FİNLAND) and computer program (Scanlt for Multiscan F.C.2.5.1) in accordance with the manufacturer's instructions. Statistical analysis was done by Statistical Package for Social Sciences for Windows 20 (IBM SPSS Inc., Chicago, IL) ve MedCalc programs. ELA and variables related to CLL were correlated with Spearman correlation anlysis test. ROC analysis and Youden index method were used to determine a cut off point for ELA. All p-values were 2-sided with statistical significance at 0.05 alpha levels.Results: In our study, we found that serum ELA levels were significantly higher in patients with CLL.Conclusions: This study highlights that ELA targeting may be a potential therapeutic option for treating CLL. [ABSTRACT FROM AUTHOR]

Bisphenol S, an industrial chemical, has raised concerns for both human and ecosystem health. Yet, health hazards posed by bisphenol S (BPS) exposure remain poorly studied. Compared to all tissues, the intestine and the liver are among the most affected by environmental endocrine disruptors. The aim of this study was to investigate the molecular effect of BPS on gene expression implicated in the control of glucose metabolism in the intestine (apelin and its receptor APJ, SGLT1, GLUT2) and in the liver (glycogenolysis and/or gluconeogenesis key enzymes (glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK)) and pro-inflammatory cytokine expression (TNF-α and IL-1β)). BPS at 25, 50, and 100 μg/kg was administered to mice in water drink for 10 weeks. In the duodenum, BPS exposure reduces significantly mRNA expression of sodium glucose transporter 1 (SGLT1), glucose transporter 2 (GLUT2), apelin, and APJ mRNA. In the liver, BPS exposure increases the expression of G6Pase and PEPCK, but does not affect pro-inflammatory markers. These data suggest that alteration of apelinergic system and glucose transporters expression could contribute to a disruption of intestinal glucose absorption, and that BPS stimulates glycogenolysis and/or gluconeogenesis in the liver. Collectively, we reveal that BPS heightens the risk of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to determine the Effects of aerobic training on Apelinergic system of heart tissue in aged rats. Methods: In this study 14 elderly wistar rats with average age of 40-50 months old, were randomly divided into two groups: control and training. Swimming training was programmed 3 days /week, 30 min/day for 8 weeks. All rats were sacrificed 48 hours after the final training session and after 24 hours of fasting myocardial tissue, apelin and its receptor levels were determined using ELISA method. Results: No significant difference was found between control and experimental group apelin heart muscle tissue there (p=0.01). Also, the apelin receptor test for heart tissue between the two groups was significant (p=0.02). Pearson correlation analysis between apelin and its receptor in the control group was statistically significant inverse linear (p=0.01), But the test for the exercise group showed no significant relationship (p= 0.44). Conclusion: It is possible that aerobic training in older people with varying levels of apelin and its receptors in heart muscle tissue, improves the cardiovascular system of the people. [ABSTRACT FROM AUTHOR]

The apelinergic system widely expressed and regulates hormone-enzyme secretion, motility, and protective mechanisms of the stomach. This system consists of the apelin receptor (APJ) and two peptides known as apela and apelin. The IR-induced experimental gastric ulcer model is a well-known and commonly used one that induces hypoxia and causes the release of proinflammatory cytokines. Expressions of apelin and its receptor APJ are induced by hypoxia and inflammation in the gastrointestinal tract. Apelin has been shown to affect angiogenesis positively, considered the most critical component of the healing process. Although it is known that apelin and AJP expressions are induced by inflammatory stimuli and hypoxia, stimulate endothelial cell proliferation and have a role in regenerative angiogenesis, no information or has been found in the literature regarding the role of APJ in the formation and healing of gastric mucosal lesions induced by I/R. So, we conducted a study to clarify the role of APJ in formation and healing mechanisms of IR-induced gastric lesions. Male Wistar rats were divided into five groups; control, sham-operated, IR, APJ antagonist treated-IR group (F13A+IR), and the healing groups. F13A was intravenously given to the animals. Gastric lesion index, mucosal blood flow, PGE 2 , NOx, 4-HNE-MDA, HO activity, and protein expressions of VEGF and HO-1 were measured. F13A application before the IR increased the mucosal injury, F13A application following the ischemia delayed the mucosal healing during the reperfusion period. Consequently, blocking apelin receptors may worsen gastric injury due to the IR and delay mucosal healing. • Chronic diseases, shock, alcohol, trauma, and stress can cause damage to the gastric mucosa. • Various defense mechanisms protect the gastric mucosa against deleterious factors. • Mucosal blood flow is vital in gastric mucosal protection against injury and during healing. • The apelinergic system comprises the APJ receptor and two ligands, Apelin and Apela. • APJ regulates gastric mucosal blood flow and may contribute to healing by increasing blood flow after gastric mucosal injury. [ABSTRACT FROM AUTHOR]

Catecholamines, in concert with fluid resuscitation, have long been recommended in the management of septic shock. However, not all patients respond positively and controversy surrounding the efficacy-to-safety profile of catecholamines has emerged, trending toward decatecholaminization. Contextually, it is time to re-examine the "maintaining blood pressure" paradigm by identifying safer and life-saving alternatives. We put in perspective the emerging and growing knowledge on a promising alternative avenue: the apelinergic system. This target exhibits invaluable pleiotropic properties, including inodilator activity, cardio-renal protection, and control of fluid homeostasis. Taken together, its effects are expected to be greatly beneficial for patients in septic shock. [ABSTRACT FROM AUTHOR]

The article comments on article "Acute Myocardial Response to Stretch: What We (don't) Know" published in the 2016 issue of the periodical which addressed the pathways for hemodynamic stress alleviation. It mentions Frank-Starling Mechanism (FSM) and Slow Force Response (SFR) are contributed in the systolic adaptation of heart. It also mentions angiotensin receptor like-1, an orphan G protein-coupled receptor, and it is able to function as a bimodal switch.

Several studies have shown the beneficial effects of (-)-epicatechin (Epi) in metabolic profile and that this flavanol is a biased ligand of the apelin receptor. The apelinergic system is expressed in adipocytes and has been related to obesity and metabolic disorders. The study aim was to evaluate the effect of Epi on apelin, on its receptor and on proteins involved in lipolysis, lipogenesis, and adipogenesis in the retroperitoneal adipose tissue of male rats descended from obese mothers. We evaluated the effect of Epi in the retroperitoneal adipose tissue of four groups of male offspring, analyzing mRNA expression and protein levels of apelin and its Apj receptor. We also analyzed, by Western Blot, the levels of AMPKα, ACC, C/EBPα, ATGL, Fas, and FABP4 of the AP2 proteins. Epi significantly elevated apelin mRNA expression and protein levels as well as its Apj receptor. Besides, the flavanol significantly promoted AMPKα phosphorylation with the concomitant reduction of Fas, and the increase of the ATGL protein. In contrast, there was an increase in the inactive phosphorylated form of ACC and a decrease in the phosphorylated active form of C/EBPα. Similarly, Epi treatment induced a reduction in the fatty acid-binding protein 4 in the C+Epi and MO+Epi groups. In conclusion, Epi increases the expression of the apelinergic system and the active phosphorylated form of AMPKα; likewise, it modifies the expression level or active form of proteins involved in lipolysis, lipogenesis and adipogenesis in the retroperitoneal adipose tissue of male offspring of obese mothers. Treatment with (-)-epicatechin in the offspring of obese rats increases Apln/Apj expression which enhances lipolysis and decreases lipogenesis and adipogenesis through AMPKα activation in retroperitoneal adipose tissue. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: This study aims to examine the relationship between the development of coronary collateral circulation and serum elabela levels., Methods: Between January 2020 and December 2021, a total of 50 control individuals (29 males, 21 females; mean age: 63.2±10.0 years; range, 52 to 73 years) with no significant coronary artery disease as confirmed by angiography (Group 1) and 100 patients (55 males, 45 females; mean age: 66.6±9.6 years; range, 56 to 75 years) with coronary artery disease were included. The patients were further divided into two equal groups according to the Rentrop classification as poor (Group 2) and good coronary collateral circulation (Group 3). All groups were compared in terms of several parameters, particularly serum elabela levels., Results: Serum elabela levels were found to be statistically higher in the group with good collateral than the other groups (p<0.05). Low serum elabela levels increased the risk of developing weak collaterals by 2.43 times., Conclusion: The elabela protein is directly related to good collateral development and can be considered a potential agent for treatment., Competing Interests: Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2023, Turkish Society of Cardiovascular Surgery.)

Background: We have investigated the effect of 8 weeks aerobic training (AT) and Ferula gummosis supplement (FG) on apelin and apelin receptor (APJ), nitric oxide (NO) and angiotensin converting enzyme (ACE) of hypertensive rats. Materials and Methods: In a experimental study, 50 adult male wistar rats were classified into five groups; 1- AT, 2- FG, 3- combination of aerobic training + Ferula Gummosa supplement (TFG), 4- nitro-L-arginine-methyl ester (L-NAME), 5- shame (control) groups (SH). The rats in the 1 to 4 groups received L-NAME (10 mg/kg, 6 times a week for 8 weeks). Also, the 1 and 3 groups experienced the training of 15 to 22 m/min for 25 to 64 minutes, 5 times a week for 8 weeks, whereas, the 2 and 3 groups received Ferula gummosis supplement (90 mg/kg, 6 times a week for 8 weeks). However, rats in 5 groups received NaCl solution. Results: At protocols resulted in a significant increase in apelin and APJ as compared to control and L-NAME groups. The TFG protocols resulted in a markedly increase in apelin, APJ and significantly decrease of ACE levels as compared to L-NAME group. Chronically administration of L-NAME resulted increased, ACE, and reduced the levels of apelin, APJ and NO, as compared to control group. Conclusion: The results in this study show that physical regular activity with and without herbal treatment induce amplification in apelin/APJ system and down-regulation blood pressure in L-NAME induced hypertension in the rat kidney tissue. [ABSTRACT FROM AUTHOR]

Apelin is an endogenous peptide ligand for G protein coupled apelin receptors (APJ orphan receptors) which are very similar to angiotensin II receptors. Apelin is expressed in most tissues of the body including hypothalamus that is responsible for regulating water and food intake, the gastrointestinal tract, the circulatory system, adipose and muscle tissues, and the immune system. The physiological actions of apelin, including food intake, has not yet been reported in birds. In this study, the effect of intracerebroventricular injection of different doses of apelin-13 was investigated on food intake in neonatal broilers at the age of five and seven days. The chicks had access to food immediately after injection and cumulative food intake was measured at half, 1, 2, 3, 4, 8 and 21 hr after injection. The 2-way ANOVA analyzed data showed that apelin-13 at dose of 1.00 μg significantly reduced food intake at 21 hr after injection in five-day old chicks. In addition, in dose of 1.50 μg, it could significantly reduce food intake at 2, 3, 4, 8 and 21 hr after injection. In seven-day-old chicks, the doses of 1.00 and 4.00 μg of apelin-13 had no effect on food intake compared to the control group. Apelin-13 at dose of 2.00 μg significantly reduced food intake at 8 and 21 hr after injection. The results of this study showed that apelin-13 had a reducing effect on food consumption in neonatal broiler chicks., Competing Interests: The authors have no conflict of interests to declare that are relevant to the content of this article., (© 2023 Urmia University. All rights reserved.)

The apelin receptor (AR or APJ) is a class A (rhodopsin-like) G-protein-coupled receptor with wide distribution throughout the human body. Activation of the AR by its cognate peptide ligand, apelin, induces diverse physiological effects including vasoconstriction and dilation, strengthening of heart muscle contractility, angiogenesis, and regulation of energy metabolism and fluid homeostasis. Recently, another endogenous peptidic activator of the AR, Toddler/ELABELA, was identified as having a crucial role in zebrafish ( Danio rerio) embryonic development. The AR is also implicated in pathologies including cardiovascular disease, diabetes, obesity, and cancer, making it a promising therapeutic target. Despite its established importance, the precise roles of AR signalling remain poorly understood. Moreover, little is known about the mechanisms of peptide-AR activation. Additional complexity arises from modulation of the AR by 2 endogenous peptide ligands, both with multiple bioactive isoforms of variable length and distribution. The various apelin and Toddler/ELABELA isoforms may also produce distinct cellular effects. Further complexity arises through formation of functionally distinct heterodimers between the AR and other G-protein-coupled receptors. This minireview outlines key (patho)physiological actions of the AR, addresses what is known about signal transduction downstream of AR activation, and concludes by discussing unique properties of the endogenous peptidic ligands of the AR. [ABSTRACT FROM AUTHOR]

Copyright of Biochemistry & Cell Biology is the property of Canadian Science Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The effect of aerobic training and Ferula gummosa supplementation (90 mg/kg) on apelinergic system and markers of cardiac stress in hypertensive rats were studied. Chronically administered l-NAME resulted in an increased level of angiotensin-converting enzyme (ACE), malondialdehyde (MDA), and high-sensitive C-reactive protein (hs-CRP), and also reduced the levels of apelin, apelin and its receptor (APJ), and nitric oxide (NO) and the total antioxidant capacity (TAC), when compared with the control group. The combination of aerobic exercise and Ferula gummosa decreased MDA and hs-CRP and significantly increased cardiac apelinergic system, NO, and TAC, when compared with the control and the l-NAME groups. A rationale for an inhibitory role and a cardioprotective effect of aerobic exercise training in the attenuation of hypertension-induced cardiotoxicity was developed. [ABSTRACT FROM AUTHOR]

Adipose tissue is an active endocrine organ that produces a variety of secretory factors involved in the initiation of angiogenic processes. The bioactive peptide apelin is the endogenous ligand of the G protein-coupled receptor, APJ. Here we investigated the potential role of apelin and its receptor, APJ, in the angiogenic responses of human endothelial cells and the development of a functional vascular network in a model of adipose tissue development in mice. Treatment of human umbilical vein endothelial cells with apelin dose-dependently increased angiogenic responses, including endothelial cell migration, proliferation, and Matrigel® capillary tubelike structure formation. These endothelial effects of apelin were due to activation of APJ, because siRNA directed against APJ, which led to long-lasting down-regulation of APJ mRNA, abolished cell migration induced by apelin in contrast to control nonsilencing siRNA. Hypoxia upregulated the expression of apelin in 3T3F442A adipocytes, and we therefore determined whether apelin could play a role in adipose tissue angiogenesis in vivo. Epididymal white adipose tissue (EWAT) transplantation was performed as a model of adipose tissue angiogenesis. Transplantation led to increased apelin mRNA levels 2 and 5 days after transplantation associated with tissue hypoxia, as evidenced by hydroxyprobe staining on tissue sections. Graft revascularization evolved in parallel, as the first functional vessels in EWAT grafts were observed 2 days after transplantation and a strong angiogenic response was apparent on day 14. This was confirmed by determination of graft hemoglobin levels, which are indicative of functional vascularization and were strongly increased 5 and 14 days after transplantation. The role of apelin in the graft neovascularization was then assessed by local delivery of stable complex apelin-targeting siRNA leading to dramatically reduced apelin mRNA levels and vascularization (quantified by hemogloblin content) in grafted EWAT on day 5 when compared with control siRNA. Taken together, our data provide the first evidence that apelin/APJ signaling pathways play a critical role in the development of the functional vascular network in adipose tissue. In addition, we have shown that adipocyte-derived apelin can be up-regulated by hypoxia. These findings provide novel insights into the complex relationship between adipose tissue and endothelial vascular function and may lead to new therapeutic strategies to modulate angiogenesis. [ABSTRACT FROM AUTHOR]

The apelinergic system, which includes the apelin receptor (APJ) as well as its two specific ligands, namely apelin and ELABELA (ELA/APELA/Toddler), have been the subject of many recent studies due to their pleiotropic effects in humans and other animals. Expression of these factors has been investigated in numerous tissues and organs—for example, the lungs, heart, uterus, and ovary. Moreover, a number of studies have been devoted to understanding the role of apelin and the entire apelinergic system in the most important processes in the body, starting from early stages of human life with regulation of placental function and the proper course of pregnancy. Disturbances in the balance of placental processes such as proliferation, apoptosis, angiogenesis, or hormone secretion may lead to specific pregnancy pathologies; therefore, there is a great need to search for substances that would help in their early diagnosis or treatment. A number of studies have indicated that compounds of the apelinergic system could serve this purpose. Hence, in this review, we summarized the most important reports about the role of apelin and the entire apelinergic system in the regulation of placental physiology and pregnancy. [ABSTRACT FROM AUTHOR]

The effects of the apelinergic system components apelin (AP) and elabela (ELA) in the regulation of human cardiovascular homeostasis, and data concerning the relationship between ELA and AP and coronary artery disease (CAD) are yet unknown. The aim of the study was the evaluation of AP, ELA and APJ-receptor levels in the plasma of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS). The study group consisted of 114 patients with CAD and 33 healthy controls. Patients were divided into two groups: with CCS (n = 30) and ACS (n = 84). Routine laboratory tests and plasma ELA, AP-17, AP-13 and APJ receptor levels were measured. Echocardiographic data were analyzed in all patients. Levels of AP-17 and ELA were significantly lower in CCS than in healthy controls and ACS patients. We demonstrated significant increase of levels of plasma apelinergic system peptides, especially ELA and AP-17 in ACS patients compared with healthy controls and CCS, suggestive of compensating up-regulation mechanisms. There is a relationship between circulating ELA and AP-17 levels and classical, biochemical markers of ischemia and left ventricular ejection faction as well. [ABSTRACT FROM AUTHOR]