Pyruvate Upregulates Hepatic FGF21 Expression by Activating PDE and Inhibiting cAMP-Epac-CREB Signaling Pathway.

Fibroblast growth factor 21 (FGF21) functions as a polypeptide hormone to regulate glucose and lipid metabolism, and its expression is regulated by cellular metabolic stress. Pyruvate is an important intermediate metabolite that acts as a key hub for cellular fuel metabolism. However, the effect of pyruvate on hepatic FGF21 expression and secretion remains unknown.

The OPG/RANKL/RANK system modulates calcification of common carotid artery in simulated microgravity rats by regulating NF-κB pathway.

Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness.

Mitochondrial-Derived Peptide MOTS-c Attenuates Vascular Calcification and Secondary Myocardial Remodeling via Adenosine Monophosphate-Activated Protein Kinase Signaling Pathway.

Introduction: Vascular calcification (VC) is a complex, regulated process involved in many disease entities. So far, there are no treatments to reverse it. Exploring novel strategies to prevent VC is important and necessary for VC-related disease intervention.

Erythropoietin attenuates vascular calcification by inhibiting endoplasmic reticulum stress in rats with chronic kidney disease.

Previous studies suggested that endoplasmic reticulum (ER) stress induced-apoptosis promoted vascular calcification (VC). Interestingly, erythropoietin (EPO), an endogenous glycoprotein, exerts multiple tissue protective effects by inhibiting ER stress and apoptosis. We investigated the role and potential mechanism of EPO on VC in chronic kidney disease (CKD) rats and cultured vascular smooth muscle cells (VSMCs).

[Capsaicin Alleviate Myocardial Ischemia Reperfusion Injury Through Attenuating Mitochondrial Oxidative Stress].

Objective: To investigate the role of capsaicin (CAP) in myocardial ischemia reperfusion injury and its underlying mechanisms.

Methods: Twentyfour adult male SD rats were randomized into 4 groups,namely the control group,ischemia reperfusion group,ischemia reperfusion with CAP group,and ischemia reperfusion with CAPZ and CAP group. Isolated rat hearts underwent Langendorff perfusion.

Intermedin1-53 Attenuates Abdominal Aortic Aneurysm by Inhibiting Oxidative Stress.

Objective: Oxidative stress plays a critical role in the development of abdominal aortic aneurysm (AAA). Intermedin (IMD) is a regulator of oxidative stress. Here, we investigated whether IMD reduces AAA by inhibiting oxidative stress.

Intermedin1-53 attenuates vascular calcification in rats with chronic kidney disease by upregulation of α-Klotho.

Deficiency in α-Klotho is involved in the pathogenesis of vascular calcification. Since intermedin (IMD)1-53 (a calcitonin/calcitonin gene-related peptide) protects against vascular calcification, we studied whether IMD1-53 inhibits vascular calcification by upregulating α-Klotho. A rat model of chronic kidney disease (CKD) with vascular calcification induced by the 5/6 nephrectomy plus vitamin D3 was used for study.

[Research Progress of Klotho].

Klotho, a newly identified anti-aging gene, can be regulated by many factors, such as calcitonin gene-related peptide, fibroblast growth factor 2 could up-regulate Klotho expression; whereas renin-angiotensin system, urinary toxins, inflammation and oxidative stress could reduce expression of Klotho. There are two forms of Klotho protein: membrane-bound Klotho and secreted Klotho. Existing studies showed that Klotho was involved in the development of many diseases, including vascular calcification, atherosclerosis, hypertension, kidney damage, hyperparathyroidism, diabetes and tumors.

Metabolic changes of H2S in smokers and patients of COPD which might involve in inflammation, oxidative stress and steroid sensitivity.

Oxidative stress and inflammation play crucial role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Most patients with COPD show a poor response to corticosteroids. Hydrogen sulfide (H2S ) has been implicated in the pathogenesis of COPD, but its expression and effects in lung tissue from COPD patients are not clear.

Thyroid hormone attenuates vascular calcification induced by vitamin D3 plus nicotine in rats.

Thyroid hormones (THs) including thyroxine (T4) and triiodothyronine (T3) play critical roles in bone remodeling. However, the role and mechanism of THs in vascular calcification (VC) have been unclear. To explore the pathophysiological roles of T3 on VC, we investigated the changes in plasma and aortas of THs concentrations and the effect of T3 on rat VC induced by vitamin D3 plus nicotine (VDN).

Possible role of fibroblast growth factor 21 on atherosclerosis via amelioration of endoplasmic reticulum stress-mediated apoptosis in apoE(-/-) mice.

Fibroblast growth factor 21 (FGF-21) is an endocrine factor that can be secreted into circulation by the liver. FGF-21 takes part in metabolic actions and is thought to be a promising candidate for the treatment of diabetes. However, the role of FGF-21 in atherosclerosis is unknown.

Cardiac sympathetic afferent reflex response to intermedin microinjection into paraventricular nucleus is mediated by nitric oxide and γ-amino butyric acid in hypertensive rats.

Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide (CGRP) and involves in the regulation of cardiovascular function in both peripheral tissues and central nervous system (CNS). Paraventricular nucleus (PVN) of hypothalamus is an important site in the control of cardiac sympathetic afferent reflex (CSAR) which participates in sympathetic over-excitation of hypertension. The aim of this study is to investigate whether IMD in the PVN is involved in the inhibition of CSAR and its related mechanism in hypertension.

Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate/protein kinase A pathway.

We previously reported that endoplasmic reticulum (ER) stress-mediated apoptosis participated in vascular calcification. Importantly, a novel paracrine/autocrine peptide intermedin1-53 (IMD1-53) in the vasculature inhibited vascular calcification in rats. But the mechanisms needed to be fully elucidated.

Ghrelin protects heart against ERS-induced injury and apoptosis by activating AMP-activated protein kinase.

Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), is a cardioprotective peptide. In our previous work, we have revealed that ghrelin could protect heart against ischemia/reperfusion (I/R) injury by inhibiting endoplasmic reticulum stress (ERS), which contributes to many heart diseases. In current study, using both in vivo and in vitro models, we investigated how ghrelin inhibits myocardial ERS.

Activating transcription factor 4 is involved in endoplasmic reticulum stress-mediated apoptosis contributing to vascular calcification.

Our previous work reported that endoplasmic reticulum stress (ERS)-mediated apoptosis was activated during vascular calcification (VC). Activating transcription factor 4 (ATF4) is a critical transcription factor in osteoblastogenesis and ERS-induced apoptosis. However, whether ATF4 is involved in ERS-mediated apoptosis contributing to VC remains unclear.

Angiotensin-(1-7) inhibits vascular calcification in rats.

Angiotensin-(1-7) [Ang-(1-7)] is a new bioactive heptapeptide in the renin-angiotensin-aldosterone system (RAAS) with potent protective effects in cardiovascular diseases, opposing many actions of angiotensin II (Ang II) mediated by Ang II type 1 (AT1) receptor. It is produced mainly by the activity of angiotensin-converting enzyme 2 (ACE2) and acts through the Mas receptor. However, the role of Ang-(1-7) in vascular calcification (VC) is still unclear.

Peroxisome proliferator-activated receptor γ ligands retard cultured vascular smooth muscle cells calcification induced by high glucose.

Peroxisome proliferator-activated receptor γ (PPARγ) and its ligands have profound effects on glucose homeostasis, cardiovascular diseases, and bone metabolism. To explore the pathophysiological roles of PPARγ in diabetes with concomitant vascular calcification, we investigated changes in PPARγ expression and the effect of the PPARγ ligands troglitazone and rosiglitazone on vascular smooth muscle cell (VSMC) calcification induced by high glucose (HG, 25 mmol/L). Compared with low glucose, HG-induced VSMC calcification, and PPARγ mRNA, protein level was decreased.

[The endocrine function of the skeleton].

Skeleton has long been recognized as a organ supporting body system and regulating metabolism of calcium and phosphorus. Recent researches found that bone cells, especially osteoblast and osteoclast, synthesize and secrete various bioactive molecules, such as bone morphogenetic proteins, growth factors, adipokines, inflammatory cytokines and cardiovascular bioactive peptides. The active factors produced by bone not only play important roles in the skeleton system per se by paracrine/autocrine pathway but also regulate energy metabolism, inflammatory process, endocrine homeostasis by endocrine pathway.