adrenomedullin and Vascular-Diseases

Adrenomedullin is a highly conserved vasoactive peptide participating in a variety of physiological and pathophysiological processes including pregnancy, embryonic development, tumor progression and regulation of vascular tone. In particular, adrenomedullin expression is widely distributed throughout the cardiovascular system including heart, lungs, blood vessels and kidneys. The observation that adrenomedullin co-localizes with its receptors suggests that the peptide may act as an autocrine and/or paracrine factor in the regulation of cardiovascular function. In this review, we described the pathophysiological changes in plasma and local adrenomedullin associated with vascular endothelial function and the signaling mechanisms involved. Recent evidence has depicted a unique role of adrenomedullin in the regulation of vascular endothelial function in part through regulation of cAMP, cGMP and intracellular Ca(2+) mobilization. This review summarized vascular endothelial actions of adrenomedullin under both physiological and pathophysiological conditions in an effort to provide guidance for the clinical application of adrenomedullin in vascular diseases.

Topics: Adrenomedullin; Animals; Drug Therapy, Combination; Endothelium, Vascular; Humans; Ligands; Protein Binding; Receptors, Adrenomedullin; Vascular Diseases; Vasodilation

A novel vasodilator, adrenomedullin (AM), which acts as an autocrine/paracrine factor in cardiovascular system, has antiproliferative and antimigrative effects. AM gene transfer prevents the development of cuff-induced vascular injury. Moreover, AM knockout mice exhibited an increase in angiotensin (Ang) II/salt loading-induced coronary arterial lesion, hypoxia-induced pulmonary vascular damage, and cuff-induced vascular injury associated with enhancement in reactive oxygen species (ROS) generation. In addition, AM expression was stimulated by ROS, and AM directly inhibits oxidative stress so that AM might be a negative feedback substance against ROS-induced organ damages. In addition, AM increases nitric oxide and ameliorates insulin resistance, leading to oxidative stress. Consequently, endogenous AM might compensatively inhibit the development of vascular diseases at least partly through an antioxidative effect.

Topics: Adrenomedullin; Animals; Cardiovascular Diseases; Humans; Insulin Resistance; Nitric Oxide; Peptides; Reactive Oxygen Species; Receptors, Adrenomedullin; Receptors, Peptide; Vascular Diseases; Vasodilation

We investigated the potential of mid-regional pro-adrenomedullin (MR-proADM) for use as a novel biomarker for arterial stiffness as the criterion for vascular failure and cardiometabolic disease (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome) compared with high-sensitivity C-reactive protein (hsCRP). Overall, 2169 individuals (702 men and 1467 women) were enrolled. Multiple regression analysis was performed to assess the association of MR-proADM and hsCRP with brachial-ankle pulse wave velocity (baPWV), adjusting for other variables. The diagnostic performance (accuracy) of MR-proADM with regard to the index of vascular failure was tested with the help of receiver operating characteristic curve analysis in the models. MR-proADM was significantly higher in participants with vascular failure, as defined by baPWV and/or its risk factors (obesity, hypertension, dyslipidemia, diabetes, and metabolic syndrome), than in control groups. Independent of cardiovascular risk factors (age, drinking, smoking, body mass index, systolic blood pressure, lipid and glycol metabolism), MR-proADM was significantly associated with baPWV, and MR-proADM showed higher areas under the curve of baPWV than hsCRP showed. MR-proADM is more suitable for the diagnosis of higher arterial stiffness as the criterion for vascular failure than hsCRP. Because vascular assessment is important to mitigate the most significant modifiable cardiovascular risk factors, MR-proADM may be useful as a novel biomarker on routine blood examination.

Topics: Adrenomedullin; Adult; Aged; Biomarkers; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Regression Analysis; Risk Factors; Vascular Diseases; Vascular Stiffness

Vascular calcification (VC) is highly associated with increased morbidity and mortality in patients with advanced chronic kidney disease. Paracrine/autocrine factors such as vasoactive peptides are involved in VC development. Here, we investigated the expression of the novel peptide intermedin (IMD) in the vasculature, tested its ability to prevent VC in vivo and in vitro, and examined the mechanism involved.. Rat VC was induced by administration of vitamin D3 plus nicotine (VDN). IMD (100 ng kg(-1) h(-1)) was systemically administered by a mini-osmotic pump. VDN-treated rat aortas showed lower IMD content and increased expression of its receptors, along with increased vascular calcium deposition and alkaline phosphatase (ALP) activity. Low IMD levels were accompanied by increased calcium deposition in human atherosclerotic plaques. In vivo administration of IMD greatly reduced vascular calcium deposition and ALP activity in VDN-treated rats when compared with vehicle treatment, which was further confirmed in cultured vascular smooth muscle cells. Concurrently, the loss of smooth-muscle lineage markers and matrix gamma-carboxyglutamic acid (Gla) protein (cMGP) in aortas was ameliorated by administering IMD to rats with VC, and the increased phosphor-Smad(1/5/8) and core binding factor alpha-1 levels in calcified vasculature were also reduced. However, the inhibitory effects of IMD on VC were eliminated upon pre-treatment with warfarin or small interfering RNA to reduce cMGP.. Reduced endogenous IMD levels are associated with increased mineralization in vivo, and administration of IMD inhibits VC development by increasing cMGP levels. IMD may be an endogenous vasoprotective factor for VC.

Topics: Adrenomedullin; Animals; Aorta; Atherosclerosis; Calcinosis; Calcium-Binding Proteins; Cell Differentiation; Cell Lineage; Disease Models, Animal; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Muscle, Smooth, Vascular; Neuropeptides; Nicotine; Nicotinic Agonists; Peptide Hormones; Phenotype; Rats; Signal Transduction; Smad Proteins; Vascular Diseases; Vitamin D; Vitamins

Topics: Adrenomedullin; Animals; Blood Pressure; Disease Models, Animal; Genetic Markers; Mice; Models, Cardiovascular; Peptides; Vascular Diseases

Topics: Adrenomedullin; Humans; Liver Transplantation; Peptides; Postoperative Complications; Radioimmunoassay; Reproducibility of Results; Vascular Diseases; Vasodilator Agents