apelin-13-peptide and Cardiovascular-Diseases

Apelin and its G protein-coupled receptor (GPCR) have emerged as a key signalling pathway in the cardiovascular system. The peptide is a potent inotropic agent and vasodilator. Remarkably, a peptide, Elabela/Toddler, that has little sequence similarity to apelin, has been proposed as a second endogenous apelin receptor ligand and is encoded by a gene from a region of the genome previously classified as 'non-coding'. Apelin is downregulated in pulmonary arterial hypertension and heart failure. To replace the missing endogenous peptide, 'biased' apelin agonists have been designed that preferentially activate G protein pathways, resulting in reduced β-arrestin recruitment and receptor internalisation, with the additional benefit of attenuating detrimental β-arrestin signalling. Proof-of-concept studies support the clinical potential for apelin receptor biased agonists.

Topics: Amino Acid Sequence; Animals; Cardiovascular Diseases; Humans; Intercellular Signaling Peptides and Proteins; Molecular Sequence Data; Peptide Hormones; Receptors, G-Protein-Coupled

This study compared the effects of nonlinear resistance training (NRT), aerobic interval training (AIT), and detraining on adipokines and cardiometabolic risk factors in middle-aged obese men. Thirty-three obese men were randomly allocated to NRT (n = 12), AIT (n = 10), and control (CON, n = 11) groups. Subjects in experimental groups performed exercise protocols 3 days per week for 12 weeks followed by a 4-week detraining period. The NRT involved 55 min of weight training with flexible periodization. The AIT consisted of running on a treadmill (4 × 4-min intervals at 90% of maximal heart rate, with each interval separated by 3 min at 65%). Peak oxygen consumption increased significantly after training compared with CON (P < 0.01), but it increased more in the AIT group than in the NRT group (P = 0.004). After detraining, peak oxygen consumption decreased significantly in both training groups (P < 0.001); however, the value in the AIT group was still higher than that in the CON group (P = 0.003). No significant changes were observed in serum levels of omentin-1 and interleukin (IL)-18 after training (P > 0.05), but omentin-1 decreased significantly in both training groups and IL-18 increased significantly in the NRT group after detraining (P < 0.05). High-density lipoprotein cholesterol (HDL-C) increased significantly after training in the AIT group compared with the CON group (P < 0.05) and returned to the pre-training level after detraining. Conversely, apelin-13 increased significantly in response to training, compared with baseline (P < 0.05), and remained unchanged after detraining. Both training regimens had similar effects on most markers; however, AIT seems to have stronger anti-coronary disease effects (as indicated by HDL-C and peak oxygen consumption) than NRT.

Topics: Adiposity; Adult; Biomarkers; Body Mass Index; Cardiovascular Diseases; Cholesterol, HDL; Cytokines; GPI-Linked Proteins; High-Intensity Interval Training; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-18; Iran; Lectins; Male; Metabolic Syndrome; Middle Aged; Obesity; Oxygen Consumption; Resistance Training; Risk Factors; Waist Circumference

Apelin has been reported to be associated with multiple physiological processes in the cardiovascular system. The aim of the present study was to investigate the effects of Apelin‑13 administration on cardiac function, hyperglycemia, insulin resistance (IR), dyslipidemia, endothelial function, inflammation and glucose metabolism in type 2 diabetic Goto‑Kakizaki (GK) rats, and compare the protective effects of Apelin‑13 with metformin or atorvastatin. In the present study, type 2 diabetes was induced in male Goto‑Kakizaki (GK) rats fed with high‑fat diet (HFD). Simultaneously, the rats were treated with metformin (350 mg/kg/d, by gavage), atorvastatin (50 mg/kg/d, by gavage) or Apelin‑13 (200 µg/kg/d, intraperitoneal injection) once daily for 4 consecutive weeks. Hemodynamic parameters were examined by RM6240BD multi‑channel physiological signal monitoring. Fasting plasma glucose (FPG), fasting insulin (FINS), homeostasis model assessment for insulin resistance (HOMA‑IR), total cholesterol (TC), triglyceride (TG), high density lipoprotein‑cholesterol (HDL‑C), low density lipoprotein‑cholesterol (LDL‑C), endothelin‑1 (ET‑1), nitric oxide (NO), constitutive nitric oxide synthase (cNOS) activity, tumor necrosis factor‑α (TNF‑α), leptin and Apelin‑12 levels were measured. Western blotting was performed to determine the levels of Apelin‑12, glucose transporter 4 (GLUT4) and phosphorylated (p)‑5'adenosine monophosphate‑activated protein kinase (AMPK) α2. It was demonstrated that Apelin‑13 decreased heart rate, left ventricular end‑diastolic pressure, FPG, FINS, HOMA‑IR, TC, TG, LDL‑C, ET‑1, TNF‑α and leptin, whereas it increased the rise and fall of maximum rate of left ventricular pressure, HDL‑C, NO, cNOS activity and Apelin‑12 compared with the GK‑HFD group. In addition, GLUT4 and p‑AMPKα2 levels in myocardial tissues were elevated by administration of Apelin‑13. This protective effect of Apelin‑13 was comparable to that of metformin or atorvastatin. Overall, the present study demonstrated that administration ofApelin‑13 may be a promising therapeutic agent for the treatment of type 2 diabetes and metabolic syndrome.

Topics: Animals; Atorvastatin; Biomarkers; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diet, High-Fat; Disease Models, Animal; Energy Metabolism; Heart Function Tests; Hemodynamics; Intercellular Signaling Peptides and Proteins; Lipid Metabolism; Male; Metformin; Oxidation-Reduction; Protective Agents; Rats