Cell death in the failing heart: role of an unnatural growth response to overload.
Hypertrophy of the overloaded heart, characterized by an increased number of sarcomeres, provides an adaptive, short-term response. However, when cardiac overload is long-standing, the hypertrophic response appears to cause shortened myocyte survival. The mechanisms responsible for the deleterious effects of chronic myocardial hypertrophy may include a maladaptive growth response of the mature heart. Because terminally differentiated adult cardiac myocytes have little or no capacity to divide, stimuli that promote growth in the overloaded adult heart cannot lead to normal cell division. Instead, overload initiates an unnatural growth response that appears to shorten cardiac myocyte survival, possibly because the same growth factors that mediate the hypertrophic response of the adult heart can also induce programmed cell death (apoptosis). The converting enzyme inhibitors and nitrates, which have growth-inhibitory as well as vasodilator effects, may improve prognosis in heart failure by inhibiting the production of transcription factors. These transcription factors stimulate both the unnatural growth response to overload and stimuli that lead to apoptosis. Since both beta-adrenergic agonists and cytokines, such as tumor necrosis factor-alpha, can stimulate production of similar transcription factors, evidence suggests that beta blockers and vesnarinone improve the prognosis in patients with heart failure possibly because of their ability to inhibit maladaptive growth.
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000328:Adult; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy / Q000503:physiopathology*; D016923:Cell Death; D016207:Cytokines / Q000276:immunology; D006801:Humans; D009206:Myocardium / Q000473:pathology; D014665:Vasodilator Agents / Q000627:therapeutic use
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016207:Cytokines; D014665:Vasodilator Agents