Korean Circ J.  2008 Oct;38(10):507-513. 10.4070/kcj.2008.38.10.507.

Bio-Molecular Markers for Cardiovascular Disease: Significance of Natriuretic Peptides and Adrenomedullin

• Horio T
• Kawano Y

• KMID: 2225714
• DOI: http://doi.org/10.4070/kcj.2008.38.10.507

Abstract

There are many established and proposed bio-molecular markers for cardiovascular disease, including vasoactive substances, substances related to inflammation and oxidative stress, and substances involved in tissue structure and remodeling. Among these substances, we focused on natriuretic peptides and adrenomedullin (AM) as clinically useful bio-molecular markers in this review. Three natriuretic peptides-atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)-play various important roles in the cardiovascular system. ANP and BNP are released from the heart and exist primarily as circulating hormones. They participate in the regulation of blood pressure and fluid levels. Plasma levels of ANP and BNP are increased in various pathological conditions such as heart failure, myocardial infarction, and hypertension with cardiac hypertrophy. BNP is now essential as a biochemical marker in managing patients with cardiovascular disease. CNP is mainly produced in vascular endothelium. It contributes to smooth muscle relaxation and growth inhibition as a local hormone, but it is also synthesized in cardiac fibroblasts and inhibits fibroblast proliferation and myocyte growth. However, the significance of plasma CNP levels remains to be elucidated. AM is widely distributed in various organs and tissues, including the cardiovascular system. Not only it is a potent vasodilator peptide, but it also has protective effects against vascular and cardiac cell injury and excessive growth. Plasma AM levels are increased in several cardiovascular diseases, including hypertension, heart failure, myocardial infarction, and atherosclerotic disease, and AM appears to be a predictive and prognostic marker in the setting of cardiovascular disease.

Keyword

Natriuretic peptide; Adrenomedullin; Cardiovascular diseases; Atherosclerosis

MeSH Terms

Adrenomedullin
Atherosclerosis
Atrial Natriuretic Factor
Biomarkers
Blood Pressure
Cardiomegaly
Cardiovascular Diseases
Cardiovascular System
Endothelium, Vascular
Fibroblasts
Heart
Heart Failure
Humans
Hypertension
Inflammation
Muscle Cells
Muscle, Smooth
Myocardial Infarction
Natriuretic Peptide, Brain
Natriuretic Peptide, C-Type
Natriuretic Peptides
Oxidative Stress
Plasma
Relaxation
Adrenomedullin
Atrial Natriuretic Factor
Natriuretic Peptide, Brain
Natriuretic Peptide, C-Type
Natriuretic Peptides

Figure

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  Fig. 1 Role of natriuretic peptides (ANP, BNP, CNP) as circulating and local hormones in the cardiovascular system. ANP: atrial natriuretic peptide, BNP: brain natriuretic peptide, CNP: C-type natriuretic peptide, GC-A: natriuretic receptor-A, GC-B: natriuretic receptor-B.

• 

  Fig. 2 A: plasma BNP levels among chronic renal failure patients divided based on left ventricular overload status.18) The subjects were divided into four groups: those without left ventricular overload (normal), those with increased preload (left ventricular end-diastolic pressure, LVEDP), those with dilated volume (left ventricular end-diastolic volume index, LVEDVI), and those with both increased preload and dilated volume. Values are presented as means±SE. B: Kaplan-Meier curves for heart failure event-free rates in the two groups, classified based on plasma BNP levels (

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  Fig. 3 Autocrine and paracrine effects of AM secreted from cardiac myocytes and fibroblasts.25) IL: interleukin, TNF: tumor necrosis factor, ECM: extracellular matrix, AM: adrenomedullin.

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  Fig. 4 Cardiovascular event-free Kaplan-Meier curves for the three groups divided based on tertiles of basal AM levels.46) Lowest tertile, basal AM <10.1 fmol/mL; middle tertile, basal AM ≥10.1 and <13.1 fmol/mL; highest tertile, basal AM ≥13.1 fmol/mL. AM: adrenomedullin.

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