Cardiac remodelling and RAS inhibition

Area of Science:

• Cardiovascular Medicine
• Pharmacology
• Renal Physiology

Background:

• Risk factors like hypertension and diabetes increase angiotensin II (Ang II) activity, contributing to cardiovascular (CV) disease and cardiac remodelling via the CV continuum.
• The renin-angiotensin system (RAS) plays a key role in CV disease pathogenesis.
• Current treatments like ACE inhibitors and ARBs reduce CV events but do not fully suppress the RAS, leading to persistent high mortality.

Purpose of the Study:

• To explore the concept of the CV continuum and the influence of the RAS.
• To examine novel pathways within the RAS.
• To highlight the need for new therapeutic approaches for complete RAS blockade.

Main Methods:

• Review of existing literature on the CV continuum, RAS, and therapeutic interventions.
• Analysis of the role of angiotensin-(1-12) and chymase in Ang II formation.
• Discussion of current and potential future therapeutic strategies.

Main Results:

• The CV continuum model suggests intervention at any stage can modify disease progression.
• Angiotensin converting enzyme inhibitors (ACE-Is) are most effective at reducing left ventricular mass.
• An 'escape phenomenon' involving chymase converting angiotensin-(1-12) to Ang II contributes to incomplete RAS suppression.

Conclusions:

• Complete blockade of the RAS is crucial for improved patient outcomes.
• Novel therapeutic targets and pathways within the RAS are required to further reduce Ang II formation.
• Targeting these novel pathways may offer additional benefits beyond current ACE-Is and ARBs.