Adrenomedullin and cardiovascular diseases

Abstract

The cardiovascular system is regulated by the autonomic nervous system, the renin-angiotensin-aldosterone system, nitric oxide (NO) and other factors including neuropeptides. Research in neurohumoral factors has led to the development of many cardiovascular drugs. Adrenomedullin (ADM), initially isolated from the adrenal gland, has diverse physiological and pathophysiological functions in the cardiovascular system. It is produced in many organs and tissues including the vasculature. ADM has numerous actions, including vasodilation, natriuresis, antiapoptosis and stimulation of NO production. It might play a protective role in various cardiovascular pathologies, and its plasma level is elevated in patients with hypertension and heart failure. Administration of ADM is a possible therapeutic approach for treating cardiovascular diseases. A number of studies have investigated the infusion of ADM in humans, which seems to be benficial in heart failure and myocardial infarction. Instead of ADM infusion, augmentation of its endogenous level is another possible strategy. Gene therapy is feasible in animal models, but its application in humans is limited. At present, the most promising clinical application of ADM is the use of the plasma level of mid-regional proadrenomedullin as a biomarker in cardiovascular diseases. It is a good marker of prognosis and survival in patients with coronary aretery disease or heart failure.

Figure 1

Factors stimulating (+) or inhibiting (−) ADM secretion from vascular smooth muscle cell (VSMC). IL, interleukin; LPS, lipopolysaccharide; TNF, tumour necrosis factor

Figure 2

ADM major signalling pathways and downstream effects. Akt, protein kinase B; Erk, extracellular signal-regulated kinase; MAPK, mitogen-activated protein kinase; PKA, protein kinase A