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Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular

G G Serneri1, M Boddi, I Cecioni

  • 1Clinica Medica Generale e Cardiologia, University of Florence, Institute of Thoracic and Cardiovascular Surgery, University of Siena, Italy.

Circulation Research
|May 23, 2001
PubMed

Insights

Cardiac angiotensin II (Ang II) generation increases with heart failure (HF) progression. Failing heart cells lose the ability to produce growth factors in response to Ang II, despite unchanged AT(1) receptor density on myocytes.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Biochemistry

Background:

  • The cardiac renin-angiotensin system (RAS) plays a crucial role in cardiovascular homeostasis.
  • Dysregulation of cardiac RAS is implicated in the pathophysiology of heart failure (HF).
  • Understanding Angiotensin II (Ang II) generation and its downstream effects in HF is vital.

Purpose of the Study:

  • To investigate cardiac Ang II generation and its relationship with left ventricular function in patients with HF.
  • To examine the expression and localization of cardiac RAS components in failing hearts.
  • To assess the responsiveness of failing myocytes to Ang II stimulation.

Main Methods:

  • Measurement of aorta-coronary sinus concentration gradients of endogenous angiotensins.
  • Analysis of angiotensinogen and angiotensin-converting enzyme mRNA levels.
  • Immunohistochemical detection of Ang II and binding studies for AT(1) and AT(2) receptors.
  • Assessment of insulin-like growth factor-I (IGF-I) and endothelin (ET)-1 synthesis in isolated myocytes.

Main Results:

  • Cardiac Ang II generation significantly increased with HF progression, predicted by end-systolic wall stress.
  • Angiotensinogen and ACE mRNA levels were elevated in HF hearts, with expression primarily in nonmyocyte cells.
  • While AT(1) receptor density on failing myocytes remained unchanged, it was reduced on failing heart membranes. Failing myocytes lost the ability to synthesize IGF-I and ET-1 in response to Ang II.

Conclusions:

  • HF progression is associated with increased cardiac Ang II formation.
  • Cardiac AT(1) receptor density on myocytes does not change in HF, but is reduced on membranes.
  • Failing myocytes exhibit impaired synthesis of IGF-I and ET-1 upon Ang II stimulation, indicating a functional deficit.

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