Fig. 11. Role of endothelial dysfunction in the progression of chronic cardiac failure. The diagram depicts the four major underlying and mutually interacting pathophysiological mechanisms.1) Hemodynamic abnormality includes cardiac dysfunction and overloading (increased pre- and afterload) with cardiac dilatation (Starling) and remodeling (hypertrophy), cardiac muscle (decreased myocardial contractility), and pump failure leading to congestive heart failure (CHF) and death. 2) Neurohormonal imbalance includes increased plasma levels of catecholamines, renin-angiotensin-aldosterone, antidiuretic hormone, atrial and brain natriuretic peptide, prostaglandins, and dopamine. 3) Cytokine activation includes overexpression and detrimental effects of various cytokines, as, e.g., tumor necrosis factor-α (TNF-α) and interleukin-1 and -6 (IL-1, IL-6), on both myocardium and vascular and cardiac endothelium. 4) Endothelial activation-dysfunction-failure involves the entire vascular endothelial system (VE dysf), but most in particular cardiac (EE and MyoCapE) endothelial dysfunction. %Percentage of cardiac output at rest exposed to VE surface. DOI: (10.1152/physrev.00017.2002)