Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders

Ishimitsu, Toshihiko; Ono, Hitoshi; Minami, Junichi; Matsuoka, Hiroaki

doi:10.1016/j.pharmthera.2006.02.004

Cited by 95 publications

(85 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Actions of adrenomedullin are generally protective to organs and tissues, from vasodilation, natriuresis, diuresis, to anti-inflammation (2). The receptors of ADM are a complex of receptor-activity modifying proteins (RAMP) and calcitonin receptor-like receptor (CRLR) (40).…”

Section: Discussionmentioning

confidence: 99%

“…The receptors of ADM are a complex of receptor-activity modifying proteins (RAMP) and calcitonin receptor-like receptor (CRLR) (40). The mechanisms of action of ADM are thought so far to be through the generation of nitric oxide via nitric oxide-cyclic guanine monophosphate pathway or through increased intracellular cyclic adenosine monophosphate which activates protein kinase A which then activates nitric oxide synthase or through phosphatidylinositol kinase -3 activation and Akt phosphorylation resulting in enhanced stimulation of endothelial nitric oxide synthase (2,38).…”

Section: Discussionmentioning

confidence: 99%

“…The gene encoding for adrenomedullin is located within the short arm of chromosome 11 (2). Measurement of mature ADM as biomarker has been previously hampered by its short plasma half-life of 22 ± 1.6 minutes, the presence of a binding protein called human adrenomedullin binding protein (AMBP-1) identified as complement factor H (3), and the immediate binding of ADM to local receptors, which had rendered its accurate measurement difficult to achieve (3,4).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Yuyun

Narayan

2015

The American Journal of Cardiology

View full text Add to dashboard Cite

Highlights-This systematic review shows that adrenomedullin is an independent predictor of death in patients with heart failure, as well as MACE and death in patients who have suffered an acute myocardial infarction.-Quantification of this peptide might contribute to improved risk stratification in settings of heart failure and myocardial infarction. ABSTRACTWe undertook this systematic review to determine the prognostic significance of adrenomedullin (ADM) in heart failure and acute myocardial infarction (AMI) patients.Given the difficulty in measuring mature ADM, its surrogate, mid-regional proadrenomedullin (MRproADM), has been used in most studies. 1 nmol/l increase in MRproADM was associated with HR for MACE ranging from 1.78 to 4.10 (CI 1.20 -10.12), while log10 of MRproADM had hazard ratios of 3.63 to 9.75 ) for death across studies in AMI patients. In conclusion, adrenomedullin is an independent predictor of death in patients with heart failure, as well as MACE and death in patients who have suffered an AMI. Quantification of this peptide might contribute to improved risk stratification in settings of heart failure and myocardial infarction.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Yuyun

Narayan

2015

The American Journal of Cardiology

View full text Add to dashboard Cite

show abstract

“…Adrenomedullin mediates its effects through its second messenger, cyclic adenosine mono-phosphate (cAMP), which, in turn, increases the production of nitric oxide (NO) [41]. Its role in cardiac failure is mostly to reduce the afterload and dilate the coronary vessels via its vasodilatory actions [42], but the exact role of adrenomedullin in causing cardiac dysfunction in cirrhosis is unclear. It is postulated that adrenomedullin may contribute to myocardial dysfunction in cirrhosis via the negative inotropic effect of NO (see the subsequent text).…”

Section: Serum Markersmentioning

confidence: 99%

Cirrhotic cardiomyopathy

2008

View full text Add to dashboard Cite

Cirrhotic cardiomyopathy is a recently recognized condition in cirrhosis consisting of systolic incompetence under condition of stress, diastolic dysfunction related to altered diastolic relaxation, and electrophysiological abnormalities in the absence of any known cardiac disease. It can be diagnosed by using a combination of electrocardiograph, 2-dimensional echocardiography, and various serum markers such as brain natriuretic factor. The underlying pathogenetic mechanisms include abnormalities in the b-adrenergic signaling pathway, altered cardiomyocyte membrane fluidity, increased myocardial fibrosis, cardiomyocyte hypertrophy, and ion channel defects. Various compounds for which levels are elevated in cirrhosis such as nitric oxide and carbon monoxide can also exert a negative inotropic effect on the myocardium, whereas excess sodium and volume retention can lead to myocardial hypertrophy. Various toxins can also aggravate the ion channel defects, thereby widening the QRS complex causing prolonged QT intervals. Clinically, systolic incompetence is most evident when cirrhotic patients are placed under stress, whether physical or pharmacological, or when the extent of peripheral arterial vasodilatation demands an increased cardiac output as in the case of bacterial infections. Acute volume overload such as immediately after insertion of a transjugular intrahepatic portosystemic shunt or after liver transplantation can also tip these cirrhotic patients into cardiac failure. Treatment of cirrhotic cardiomyopathy is unsatisfactory. There is some evidence that b-blockade may help some cirrhotic patients with baseline prolonged QT interval. Long-term aldosterone antagonism may help reduce myocardial hypertrophy. Future studies should include further elucidation of pathogenetic mechanisms so as to develop effective treatment strategies.

show abstract

“…Adrenomedullin exhibits protective effects on the heart and the vasculature [44]. The stable midregional part of its prohormone, MR-proADM, is elevated in various cardiovascular pathologies and has been shown to be strongly predictive of mortality in populations with cardiovascular disease, especially heart failure [45] but also AMI [46].…”

Section: Mid-regional Part Of the Prohormone Of Adrenomedullinmentioning

confidence: 99%

Acute coronary syndrome – the present and future role of biomarkers1)

Lindahl¹

2013

Clinical Chemistry and Laboratory Medicine

View full text Add to dashboard Cite

Over the past two decades there have been dramatic changes in the diagnosis, treatment and prognosis of acute coronary syndrome (ACS). Several new treatment modalities have been added and the prognosis has improved dramatically. Biomarkers play a crucial role in the management of ACS. At present, cardiac troponin is the biomarker of choice for diagnosis of acute myocardial infarction (AMI). Currently, there are no other biomarkers, which can compete, neither regarding specificity nor regarding early sensitivity. However, there is still a clinical need of a biomarker able to reliably rule-in or rule-out AMI immediately on admission. MicroRNAs seem to be promising new candidates for diagnostic purposes. The optimal combination of biomarkers and new imaging techniques is another important area for research. The list of biomarkers associated with an adverse prognosis in ACS is long. However, for most of them it has been very difficult to prove an added clinical value. Only cardiac troponin, and to some degree also B-type natriuretic peptides, is widely used in clinical practice for risk assessment. Among new markers, growth differentiation factor 15 and the midregional part of the prohormone of adrenomedullin, have shown some promising results. Since the renal function is assessed in clinical routine, also markers of the renal function have gained increasing interest. Cardiac troponin has been proven useful for selection of antithrombotic, antiplatelet and invasive treatment. Besides cardiac troponin, no other markers have consistently been shown to be useful for selection of specific treatments.

show abstract

Pathophysiologic and therapeutic implications of adrenomedullin in cardiovascular disorders

Cited by 95 publications

References 200 publications

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Cirrhotic cardiomyopathy

Acute coronary syndrome – the present and future role of biomarkers1)

Contact Info

Product

Resources

About