Irrespective of the causes or the clinical manifestations of chronic heart failure (CHF), or even the criteria used to define it, one fact of the syndrome is irrefutable:CHF is a progressive disease, carries a poor long term prognosis and mortality rates remain high despite all the currently available therapy [1,2]. There is a general acceptance that, as heart disease progresses into CHF, cardiac function further deteriorates and symptoms become manifest. Although researches produce an ever-changing picture of the syndrome, it is now clear that CHF can no longer be considered a contractile disorder or a disease of the heart alone. Clinical manifestations are the result of changes to the heart’s cellular and molecular components and to the mediators that drive homeostatic control, particularly (i.e. neurohormones and cytokines). Clinical data indicate that therapeutic intervention aimed solely at correcting hemodynamic abnormalities (i.e. those offering symptomatic relief or improved hemodynamics) do not necessarily slow heart failure progression or reduce mortality [1–3]. On the contrary, interventions modulating the neurohormonal activation (i.e. angiotensin converting enzyme (ACE) inhibition, betablockade and anti-aldosterone therapy) are known to slow progression of the syndrome and to reduce morbidity and mortality [1,2,4–7]. From a pure clinical perspective, progression of the disease is not detectable, particularly if not immediately associated to symptoms deterioration. There is, however, general acceptance that as heart failure progresses, the shape of the heart changes, its size increases and cardiac function deteriorates. Although different terms have been used to describe it, cardiac remodeling encompassesmanychanges associated with progressive heart failure. Thus, cardiac remodeling is recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in CHF of all aetiologies. Currently, the origin of cardiac remodeling is thought to be multifactorial and remains unknown. A complex interaction between myocyte hypertrophy and apoptopic death finally leading to the reshaping of the left ventricle is believed to be of great importance. The triggers for such a mitotic and anti-mitotic behaviour are discussed. Since neurohormones and cytokines can both enhance cell proliferation and death, they constitute an interesting field of investigation in respect to this. This paper provides an overview of key concepts about cardiac remodeling, especially focusing on the role that neurohormones and cytokines are thought to play through cell hypertrophy and apoptosis.
Neurohormones, cytokines and programmed cell death in heart failure: A new paradigm for the remodeling heart
CECONI, Claudio;FERRARI, Roberto
2001
Abstract
Irrespective of the causes or the clinical manifestations of chronic heart failure (CHF), or even the criteria used to define it, one fact of the syndrome is irrefutable:CHF is a progressive disease, carries a poor long term prognosis and mortality rates remain high despite all the currently available therapy [1,2]. There is a general acceptance that, as heart disease progresses into CHF, cardiac function further deteriorates and symptoms become manifest. Although researches produce an ever-changing picture of the syndrome, it is now clear that CHF can no longer be considered a contractile disorder or a disease of the heart alone. Clinical manifestations are the result of changes to the heart’s cellular and molecular components and to the mediators that drive homeostatic control, particularly (i.e. neurohormones and cytokines). Clinical data indicate that therapeutic intervention aimed solely at correcting hemodynamic abnormalities (i.e. those offering symptomatic relief or improved hemodynamics) do not necessarily slow heart failure progression or reduce mortality [1–3]. On the contrary, interventions modulating the neurohormonal activation (i.e. angiotensin converting enzyme (ACE) inhibition, betablockade and anti-aldosterone therapy) are known to slow progression of the syndrome and to reduce morbidity and mortality [1,2,4–7]. From a pure clinical perspective, progression of the disease is not detectable, particularly if not immediately associated to symptoms deterioration. There is, however, general acceptance that as heart failure progresses, the shape of the heart changes, its size increases and cardiac function deteriorates. Although different terms have been used to describe it, cardiac remodeling encompassesmanychanges associated with progressive heart failure. Thus, cardiac remodeling is recognised as an important aspect of cardiovascular disease progression and is, therefore, emerging as a therapeutic target in CHF of all aetiologies. Currently, the origin of cardiac remodeling is thought to be multifactorial and remains unknown. A complex interaction between myocyte hypertrophy and apoptopic death finally leading to the reshaping of the left ventricle is believed to be of great importance. The triggers for such a mitotic and anti-mitotic behaviour are discussed. Since neurohormones and cytokines can both enhance cell proliferation and death, they constitute an interesting field of investigation in respect to this. This paper provides an overview of key concepts about cardiac remodeling, especially focusing on the role that neurohormones and cytokines are thought to play through cell hypertrophy and apoptosis.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
